Cancer Epidemiology - Articles in Press

Print news coverage of cancer: What prevention messages are conveyed when screening is newsworthy? - Uncorrected Proof

Katherine Clegg Smith, Elizabeth Edsall Kromm, Ann Carroll Klassen — 2010-03-02

Abstract: Background: Americans are generally favorable towards cancer screening, but fatalistic about cancer prevention. News coverage shapes perceptions of cancer control in meaningful ways, but there is little consensus as to the impact of news on our understanding of and engagement in cancer screening practices. Our analysis of cancer screening-related print news coverage during a four month period in 2005 suggests that the newsworthiness of new screening technologies may undermine public confidence in currently available and effective secondary prevention programs, while promoting tests whose effectiveness is debated or not yet established. Methods and results: We conducted a structured text analysis of 517 cancer-related news articles from 15 leading daily newspapers and a subsequent qualitative analysis of the 79 screening news articles. Screening articles were analyzed for content related to criteria for screening effectiveness. Content patterns for each type of screening and cancer were also noted. News coverage consistently conveyed screening as important and highlighted the need to protect and expand access to screening. At the same time, to the extent that story content was framed by the newsworthiness of new tests and technologies this often indirectly called into question effective and established protocols and programs without providing any actionable alternative. Conclusion: This analysis revealed unexpected messages about screening that are potentially problematic for cancer control. The cancer control community should continue efforts to understand and shape news coverage of screening in order to promote balanced and action-oriented content. Research has shown that Americans hold conflicting views regarding cancer—having a favorable opinion of screening while simultaneously feeling fatalistic about prevention. Our analysis of print news stories on cancer screening suggests that the determination of screening's “newsworthiness” is related to newly developed tests and protocols, which may create demand for new tests whose effectiveness is unknown and undermine confidence in established and effective screening programs.

Haplotype analysis of p53 polymorphisms: Arg72Pro, Ins16bp and G13964C in Tunisian patients with familial or sporadic breast cancer - Uncorrected Proof

2010-03-02

Abstract: Background: The p53 polymorphisms have been extensively studied as putative breast cancer susceptibility variants. The present study was undertaken to investigate the association of p53 Arg72Pro, Ins16bp and G13964C polymorphisms and their haplotypes with breast cancer risk in Tunisian women. Methods: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 159 patients and 132 controls. Results: The G13964C intronic variant was significantly associated with familial breast cancer risk (p=0.0018) while the genotypic distribution was similar for p53 Arg72Pro and Ins16bp in patients and controls. Moreover, the (NoIns-C), (Arg-C) and (NoIns-Arg-C) haplotypes were significantly associated with familial breast cancer risk (p=0.0021, p=0.0096 and p=0.0084, respectively) while there was a trend of association between the (Ins-Arg) and (Ins-Arg-G) haplotypes and the risk of sporadic breast cancer. Only the G/C genotype as well as the (NoIns-C) haplotype remained significant after correction for multiple testing. Conclusion: Our data revealed an association between the G/C genotype and the (NoIns-C) haplotype and the risk of familial breast cancer in Tunisian women. However, these observations need to be confirmed due to the limited statistical power of our study and the small number of cases.

Do the Japanese feel more suspicious about cancer registration than the British? - Uncorrected Proof

Tomohiro Matsuda, Tomomi Marugame, Wakiko Ajiki, Tomotaka Sobue — 2010-02-25

Abstract: Background: Cancer registration is indispensable, providing useful statistical measures for the appropriate evaluation of cancer control programs and medical treatment or screening. Methods: Following the British national survey on attitudes toward cancer registration, we conducted an investigation to correctly evaluate the general opinion of the Japanese population in this regard. We randomly recruited 3000 men and women aged 20–69 years from a research database. Results: Only 4% of all respondents had heard about the cancer registry system before the investigation. However, 77% of respondents thought that cancer registration was useful. Forty-three percent of respondents answered, regardless of the strictness of the data protection, that privacy had been violated if the registration occurred without an individual explanation. Compared with the British survey results, Japanese people seemed to be more suspicious about the largely unknown system of cancer registry. Nonetheless, it is noteworthy that Japanese respondents did not show active opposition to cancer registration; they tended to choose “I don’t know” instead of “no” to questions asking if they supported the registry system. Multivariate analysis showed that male sex, older age, and living in the southern region were the factors significantly associated with support for cancer registration. Conclusions: We can seek society's understanding toward cancer registration by actively utilizing information from cancer registries, by using examples of how data are actually used that have wide appeal, and by educating the public on how the data are treated under the complete privacy policy.

Meta-analysis of epidermal growth factor 61A>G polymorphism and cancer risk - Uncorrected Proof

Yan-Mei Zhang, Chao Cao, Kun Liang — 2010-02-25

Abstract: Numerous studies have investigated the risk of cancer associated with the polymorphism of epidermal growth factor (EGF) 61A>G, but the results have been inconsistent. To drive a more precise estimation of association between this polymorphism and risk of cancer, we performed a meta-analysis of 5578 cancer cases and 7306 controls from 23 published case–control studies. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. This meta-analysis showed significant effect of EGF 61A>G on cancer risk (GG vs. AA: OR=1.34, 95%CI=1.05–1.72; GG vs. GA+AA: OR=1.23, 95%CI=1.03–1.47; GG+GA vs. AA: OR=1.18, 95%CI=1.02–1.38). In subgroup analysis, significant increased risk was found in gastric cancer and glioma in additive model (OR=1.54, 95%CI=1.13–2.12; OR=1.69, 95%CI=1.21–2.37) and in recessive model (OR=1.29, 95%CI=1.10–1.52; OR=1.54, 95%CI=1.16–2.04). The results suggest that the EGF 61G allele is a risk factor of cancer, especially for gastric cancer and glioma.

Prevalence and correlates of recent and repeat mammography among California women ages 55–79 - Uncorrected Proof

William Rakowski, Roberta Wyn, Nancy Breen, Helen Meissner, Melissa A. Clark — 2010-02-25

Abstract: Objective: Data on repeat mammography rates are less available than for recent screening. Two large, population-based state surveys provide the opportunity to investigate repeat and recent mammography prevalence and correlates among California's diverse population. Methods: Data were from women aged 55–79, using the 2001 and 2005 California Health Interview Surveys. The study assessed the prevalence and correlates of recent mammography (within the past two years) and repeat mammography (mammogram within the past two years and 3–11 mammograms within the past six years). Results: Prevalence was 82.4% (recent) and 73.8% (repeat) in 2001, and 87.1% (recent) and 77.5% (repeat) in 2005. Correlates of lower rates were insurance status, no usual source of care, being a smoker, age 65–79, being Asian with no English proficiency, being never married, and lower absolute risk for breast cancer. Especially low ratios of repeat-to-recent mammography existed for the uninsured, and those using the emergency room or with no source of care. Unexpected findings in which unadjusted results were inconsistent with multivariable adjusted results occurred for Latinas with no English proficiency and women at 200–299% of poverty level. Conclusions: Several groups of women in California remain at-risk of lower mammography utilization. However, investigators should also be alert for instances where multivariable analyses seem particularly discrepant with crude rates.

Male pattern baldness and prostate cancer risk in a population-based case–control study - Uncorrected Proof

Jonathan L. Wright, Stephanie T. Page, Daniel W. Lin, Janet L. Stanford — 2010-02-22

Abstract: Purpose: Male pattern baldness (MPB) and prostate cancer (PCa) share commonality as prevalent, heritable and androgen-related conditions. Studies exploring the relationship between the two conditions have been inconclusive. Using a population-based, case–control study of PCa, we explore the relationship between early-onset MPB and PCa risk. Methods: Cases were men aged 35–74 diagnosed with PCa between 2002 and 2005 in King County, Washington. Controls were frequency matched by age and identified by random digit dialing. Hair pattern at age 30 and at 1 year prior to diagnosis (cases) or reference date (controls) was determined using showcards. PCa risk associated with balding was assessed with logistic regression. Results: Data from 999 cases of PCa and 942 controls were analyzed. Hair loss at age 30 was more common in controls (25.2%) than cases (19.8%, p=0.005), and those with hair loss at age 30 had a 29% relative risk reduction for PCa (OR 0.71, 95% CI 0.56–0.91). No risk reduction was seen for men only reporting hair loss at referent age (OR 0.90, 95% CI 0.73–1.12). In men aged >60 at referent date, the risk reduction was greater for men with hair loss at age 30 from both the top of head and forehead (OR 0.55, 95% CI 0.33–0.93). Conclusion: Early-onset MPB was associated with a reduced relative risk of PCa in this population-based study. Further research into a possible mechanistic link between these prevalent and androgen-related conditions is warranted.

Smoking (active and passive), N-acetyltransferase 2, and risk of breast cancer - Uncorrected Proof

Michael S.C. Conlon, Mary Bewick, Kenneth Johnson, Robert Lafrenie, Allan Donner — 2010-02-18

Abstract: Background: The relationship between smoking and breast cancer remains controversial. The study aim was to assess the relationship of passive and active smoking to breast cancer risk by N-acetyltransferase 2 (NAT2) phenotype, using a comprehensive assessment of both passive and active smoking. Methods: We undertook a population-based case–control study in Northeastern Ontario, Canada of 347 women diagnosed (2002–2004) with breast cancer and 775 population-based controls. The mailed study package included a questionnaire requesting information about established breast cancer risk factors, passive and active smoking, and a buccal swab for genetic analyses. Results: Among never-active smokers, a long duration of passive smoking was associated with an increased risk of breast cancer (odds ratio (OR) 1.86 (95% confidence interval (95% CI) 1.01–3.44) (test for trend (p=0.07)); that risk was more elevated for NAT2 slow acetylators (OR 2.76, 95% CI 1.16–6.59) (and highest in extremely slow acetylators), but not elevated for NAT2 fast acetylators (OR 1.17, 95% CI 0.42–3.23)). Among active smokers more than 20 pack-years of smoking was associated with an OR of 1.34 (95% CI 0.92-1.96); more elevated among NAT2 fast acetylators OR 1.93 (95% CI 1.01–3.69) but not elevated among NAT2 slow acetylators. Women who were NAT2 fast acetylators in the highest quartile for duration of active smoking had an OR of 2.74 (95% CI 1.42–5.27), with a significant test of trend (p=0.005). Conclusions: These findings suggest that passive and active smoking may be related to breast cancer, and the effect may be differentially modified by NAT2 phenotype. Further research into the genetic modification of a breast cancer–smoking relationship may help to reconcile earlier discrepant findings.

Effects of deprivation on the geographical variability of larynx cancer incidence in men, Girona (Spain) 1994–2004 - Uncorrected Proof

2010-02-17

Abstract: Objective: To assess the association between the incidence of larynx cancer and socioeconomic conditions in the province of Girona from a spatial viewpoint. Materials and methods: Incidence cases of larynx cancer (CL) in 1994–2004 were provided by the Girona Cancer Registry. A census tract (CT) was assigned to all patients. Socioeconomic data were extracted from the 2001 Census. A deprivation index for each CT was obtained by principal component analysis, using four socioeconomic indicators. The standardised incidence ratio (SIR) was calculated using the CL incidence rates in the men of the province of Girona assuming a Poisson distribution. Relative risk was obtained applying the Besag, York and Mollié model. The deprivation index was introduced into the model and was categorised in quartiles. Results: Four hundred and seventy-six incident cases in men were registered. CTs in the lowest deprivation index had a lower risk of larynx cancer, with a risk increase in the higher quartiles. In the highest quartile it was 1.91 times greater than in the lowest. This association was significant when the whole province was considered. Discussion: The deprivation index explains only part of the geographical variability of CL incidence. Other risk factors without spatial structure may contribute to this explaination.

Geographic variation in breast cancer care in Switzerland - Uncorrected Proof

S. Ess, A. Savidan, H. Frick, Ch. Rageth, G. Vlastos, U. Lütolf, B. Thürlimann — 2010-02-15

Abstract: Purpose: Regional disparities in breast cancer outcomes have been reported in Switzerland. The purpose of this study is to investigate geographic variation in early diagnosis and management of breast cancer. Methods: We used data from a representative sample of 4820 women diagnosed with invasive breast cancer between January 1, 2003 and December 31, 2005 identified by seven Swiss population based cancer registries. We collected retrospectively detailed information on mode of detection, tumor characteristics and treatments. Differences across geographic regions were tested for statistical significance using chi-square tests and uni- and multivariate logistic regression. Results: Considerable disparities in early detection and management of early breast cancer were found across regions. In particular, the proportion of early detected cancer varied from 43% in Valais to 27% in St. Gallen-Appenzell. Mastectomy rates varied from 24% in Geneva to 38% in St. Gallen-Appenzell and Grisons-Glarus. Higher reconstruction rates were observed in regions with lower rates of mastectomy. The use of sentinel node procedure in patients with nodal negative disease was high in Geneva and low in Eastern Switzerland. Differences in compliance with recommendations on the use of endocrine therapy and chemotherapy were less pronounced but statistically significant. Conclusions: This analysis shows considerable geographic variation in breast cancer care in a health system characterized by high expenditures, universal access to services and high decentralization. Further study into the causes and effects of this variation on short- and long term patient outcomes is needed.

Melanocortin 1 receptor (MC1R), pigmentary characteristics and sun exposure: Findings from a case–control study of diffuse large B-cell and follicular lymphoma - Uncorrected Proof

2010-01-25

Abstract: The relationship between skin cancer and non-Hodgkin lymphoma (NHL) suggests common genetic, host or environmental causes. Ultraviolet radiation (UVR), pigmentary characteristics have been linked with both malignancies, and for skin cancer, the melanocortin 1 receptor (MC1R) which influences pigmentation has also been implicated. This paper reports on the relationship between MC1R, skin, hair and eye colour, time spent outdoors, and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Persons carrying MC1R homozygote variant alleles at R151C, R160W, D294H and D84E were more likely to have fair skin, red hair and to spend less time outdoors than those who did not. The variant allele at V92M was associated with FL (odds ratio (OR)=1.61, 95% confidence interval (CI) 1.08–2.39) and the r:wild type genotype with DLBCL (OR=0.58, 95% CI 0.38–0.89). Interactions between MC1R genotypes and skin colour influenced DLBCL risk; the RR genotype increased risk in individuals with medium or dark skin, based on 5 cases and no controls, but decreased risk among those of fair skin. On the whole, DLBCL and FL risk were not related to genetic variation in MC1R, pigmentation or time spent outdoors.

Renal cell cancer in Israel: Sex and ethnic differences in incidence and mortality, 1980–2004 - Uncorrected Proof

2010-01-21

Abstract: Background: The causes of renal cell cancer (RCC) remain largely unexplained. While the incidence is generally higher in men than in women, little has been reported on ethnic differences. We examine trends in RCC incidence and mortality rates among Israeli Arab and Jewish populations and compared with the rates in other countries. Methods: Age-adjusted RCC incidence and mortality rates in Israel, during 1980–2004, were calculated by sex and population group, using the National Cancer Registry. They were compared with the United States based on the Surveillance Epidemiology and End Results [SEER] program and the IARC database for international comparisons. Results: While RCC incidence rates in Israel are similar to the United States and the European average, the rates are significantly higher among Israeli Jews than Arabs. Men are affected more than women. Incidence rates over the last 24 years have increased among all men and Jewish women, but not among Arab women. Among men, the incidence rate ratio for Jews to Arabs declined from 3.96 in 1980–1982 to 2.34 in 2001–2004, whereas for women there was no change. The mortality rates were higher among Jews than Arab and among men than women. There were no significant change in the mortality rates and rate ratios. Conclusions: Our findings demonstrate marked ethnic differences in RCC in Israel. The lower incidence among Arabs stands in contrast to the higher prevalence of potential risk factors for RCC in this population group. Genetic factors, diet and other lifestyle factors could play protective roles.

CYP2C9 genotype does not affect risk of tobacco-related cancer in the general population - Uncorrected Proof

Diljit Kaur-Knudsen, Børge Grønne Nordestgaard, Stig Egil Bojesen — 2010-01-21

Abstract: Background: CYP2C9 enzymes are important in the metabolism of procarcinogenic chemicals such as polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke. Two functional variants in the CYP2C9 gene (CYP2C9*2 and CYP2C9*3) are known to be associated with decreased enzyme activity towards tolbutamide and warfarin, while this has not been investigated for PAHs. We hypothesised that these two variants in the CYP2C9 gene influence risk of tobacco-related cancer. Methods: In a prospective study of the general population (n=10 392) with 60 years of follow-up, the Copenhagen City Heart Study, we associated two variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) with risk of tobacco-related cancer and all cancer. All results were re-tested in a cross-sectional study of the general population (n=36 856), the Copenhagen General Population Study. Results: We found no association between any of the CYP2C9 genotypes and risk of tobacco-related cancer, individual tobacco-related cancers, or all cancer. For the combined carriers (any CYP2C9*2 or CYP2C9*3 heterozygotes or homozygotes) vs. non-carriers we had 90% statistical power to exclude measures of relative risks below/above 0.8/1.2 and 0.9/1.1 in the Copenhagen City Heart Study and below/above 0.8/1.3 and 0.9/1.1 in the Copenhagen General Population Study for tobacco-related cancer and all cancer, respectively. Conclusion: Genetic variations in CYP2C9 do not affect risk of tobacco-related cancers.

Immunoprecipitation of nucleosomal DNA is a novel procedure to improve the sensitivity of serum screening for the p16 hypermethylation associated with colon cancer - Uncorrected Proof

2010-01-20

Abstract: Background: We developed a novel method of methylation-specific PCR (MSP) using immunoprecipitation with anti-histone antibody (IP-MSP) to efficiently detect serum methylated DNA tightly bound to de-acetylated histones. Materials and methods: The detection limit of IP-MSP for p16 methylation was determined with a standard made by cell line (SKCO-1) lysate. p16 methylation of tumor and/or serum of 51 colorectal cancers and 10 adenoma patients, and 10 healthy volunteers was detected with conventional MSP or IP-MSP. Results: IP-MSP detected p16 methylation from 0.5pg/μl of the cell lysate. The sensitivity of IP-MSP for detecting serum p16 methylation in 27 patients with tumors characterized by p16 methylation was significantly higher than that with conventional method (81% versus 59%), particularly in Stage II patients (91% versus 45%). IP-MSP detected no p16 hypermethylation in sera of adenoma patients and volunteers. Conclusions: IP-MSP is thus considered to be a promising procedure to detect serum methylated DNA in colorectal cancer patients.

Genistein and daidzein act on a panel of genes implicated in cell cycle and angiogenesis by PCR arrays in human prostate cancer cell lines - Uncorrected Proof

2010-01-18

Abstract: Background: The prostate cancer most frequently affects men. The ethnic origin and family antecedents of prostate cancer are established as risk factors. The genetic factors associated with environmental factors such as the nutrition also play a role in the development of the cancer. Epidemiological studies showed that the Asian populations exhibited an incidence of prostate cancer markedly subordinate by comparison with the Western populations. This would be explained partially by their important consumption of soy. Both main phytoestrogens of soy, the genistein and the daidzein, present anti-proliferative properties. Methods: For that purpose, we used different prostate cancer cell lines (LNCaP, DU 145, PC-3) and, by flow cytometry, we determined the concentration of phytoestrogens inducing a cell cycle arrest and the required time of incubation. Results: Then, the effects of 40μM genistein or 110μM daidzein for 48h were determined and studied on the expression of genes involved in the human cell cycle and angiogenesis and conducted by SYBR green quantitative PCR. Conclusion: We demonstrated modulations of cyclin-dependent kinase-related pathway genes, DNA damage-signaling pathway and a down-regulation of EGF and IGF.

The use of bioimpedance in the detection/screening of tongue cancer - Uncorrected Proof

2010-01-15

Abstract: Oral cancers are the 11th most common malignancy reported worldwide, accounting for 3% of all newly diagnosed cancer cases, and one with high mortality ratios among all malignancies. The objectives of this study were therefore to study the electrical properties of cancerous tongue tissue and normal tongue tissue, as well as to investigate a new approach for low-cost, noninvasive, and real-time screening of oral cancer. Twelve tongue cancer patients and twelve healthy subjects participated in this study. A disposable probe with four silver electrodes was used to measure the electrical properties of patient's and healthy subject's tongue tissues at six different frequencies, which were 20Hz, 50kHz, 1.3MHz, 2.5MHz, 3.7MHz and 5MHz. The amplitude of the applied voltage was limited to 200mV. Four measurement parameters of impedance, phase angle, real part of impedance, and imaginary part of impedance of tongue were assessed to see if significant difference in values obtained in patient's and healthy subject's tongue tissues existed. Intraclass correlation coefficient showed that all measurements had good reliability and validity (ICC>0.95 for all measurements). Significant differences were found at 20Hz (p<0.05–0.001 for the four measurement parameters) and 50kHz (p<0.001 for the four measurement parameters) between patient's and healthy subject's tongue tissues. In conclusion, bioimpedance at a particular frequency is a potentially promising technique for tongue cancer screening.

Prevalence of human papillomavirus infection among young women in North India - Uncorrected Proof

2010-01-06

Abstract: Background: The number of women infected with human papillomavirus (HPV) and the distribution of the HPV genotypes vary across populations and with age. Objective: To determine the prevalence and genotype distribution of HPV in young married women aged 16–24 years. Methods: 1300 women residing in an urban slum in Delhi donated samples of exfoliated cervical cells that were collected by the Digene® kit and tested for the presence of HPV DNA by two techniques in parallel, i.e., PCR using PGMY consensus primers for all HPV types and the Digene HPV test (Hybrid Capture 2 (HC2) Probe B for high-risk (hr) types. Genotyping was done on all HPV positive samples using the reverse line blot assay. Results: HPV infection was detected in 91/1300 (7%) samples by PCR and 110/1300 (8.4%) samples by HC2. Genotyping identified 20 high-risk and 11 low-risk types. HPV16 was the commonest high-risk type (3%) followed by HPV52 (1.2%) and HPV51 (0.8%). Among low-risk types, HPV62 was the commonest (0.8%), followed by HPV84 and HPV89 (0.5% each). Multiple infections were found in 3% of the samples. Conclusion: A wide spectrum of HPV genotypes is seen in this young population. Knowledge about HPV types prevalent in communities in different regions of India would be useful in devising the optimum strategy for cervical cancer prevention.

Public perceptions of the harms and benefits of testicular cancer education: A qualitative study - Uncorrected Proof

Ruth E.C. Evans, Alice E. Simons, Jane Wardle — 2009-12-25

Abstract: Background: The value of testicular cancer (TC) education, and in particular advice on testicular self-examination (TSE), has been widely debated by health professionals. One concern centres on its potential to cause unnecessary anxiety among the target population. Views outside the health professional community about TC education's potential benefits and harms have not previously been described. The objective of this study was to investigate the range of views expressed by specific groups thought to have an interest in provision of TC education. Methods: One-to-one, in-depth interviews with 37 men and women were completed. Participants included TC patients, men with no prior diagnosis of TC, and parents and teachers of adolescent boys. Verbatim transcripts were analysed using the Framework approach to produce a thematic description of views expressed. Results: Participants were unanimously in favour of TC education. Key perceived benefits included earlier cancer detection through increasing knowledge of symptoms leading to better treatment outcomes, and motivating help-seeking by reducing emotional barriers such as fear of cancer or embarrassment. Anxiety was acknowledged as a possible harm but was not expected to be widespread or serious. Conclusion: TC education is viewed favourably by members of the public likely to be interested in its provision. Education's potential to cause anxiety was not considered a disincentive to promoting disease awareness.

Prevalence and genotype identification of human papillomavirus in women undergoing voluntary cervical cancer screening in Molise, Central Italy - Uncorrected Proof

2009-12-25

Abstract: We examined the prevalence of HR- and LR-HPV by Linear Array genotyping test in 299 women aged 18–63 years who consecutively visited Molise Region main hospitals for routine Pap smear between February and August 2008. Ninety women were positive for any HPV (30.1%), and 66 for any HR-HPV (22.1%). The most prevalent HR-HPV types were HPV 16 (22.2% of all women with HPV infection), HPV 53 (14.4%), and HPV 66 (14.4%). HPV infections increased from 15.8% in the 18–20 years group to 50.0% in the 21–23 years group and then decreased to 9.1% in those aged 50 years or more (p=0.008). Multiple HPV infections were observed in 15.7% of the study sample (52.2% of all HPV positive). There is a significantly higher prevalence of multiple infections in 18–32 years group women (24.5%) compared with females aged 33 years or more (6.8%) (p<0.005). Current smokers were at increased risk of HPV infection (44.2% of HPV infections compared with 23.5% in never smokers, and 25.3% of multiple HPV infections compared with 11.3%; p=0.001). HR-HPV infections were higher in women never been pregnant (27.1% compared with 7.7%; p=0.001). Oral contraceptive use was completely unrelated to infection. Among the 122 women who had both cytological examination and HPV results, multiple HR-HPV types were found in 36.8% of those with abnormal cervical findings, and in 13.6% of those with normal cervical findings (p=0.05). The results of the present investigation provide further evidence for the notion that cervical HPV infection is more widespread than previously suggested.

Fibrous pseudotumors of tunica albuginea, tunica vaginalis and epididymis: Report of two cases - Uncorrected Proof

Serdar Ugras, Cemile Yesil — 2009-11-05

Abstract: We describe two rare cases of fibrous pseudotumor of the paratesticular region. In the first case, five nodules arising from the tunica albuginea of right testicle causing scrotal, enlargement raising after urinary tract infection were seen. In the second case, multiple nodules arising tunica albuginea, tunica vaginalis and epididymis raising after left varicocelectomy operation were observed. The histology showed a paucicellular fibroblastic proliferation of cells within a hyalinized collagenous fibrous stroma containing numerous thin-walled blood vessels accompanied by lymphocytes and plasma cells in tumor tissues in both cases. Tumors in both cases were successfully resected. After operation, both patients had an uneventful recovery without any complications.

African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer - Uncorrected Proof

Ikuko Kato, Michelle Cichon, Cecilia L. Yee, Susan Land, Jeannette F. Korczak — 2009-11-05

Abstract: Background: African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer. Methods: A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action. Results: The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio (OR)=2.34, 95% confidence interval (CI) 1.23–4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P=0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR=3.00, 95%CI 1.29–6.99). Conclusion: These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases.

Antioxidant activity in essential oils of Cnidium officinale makino and Ligusticum chuanxiong hort and their inhibitory effects on DNA damage and apoptosis induced by ultraviolet B in mammalian cell - Uncorrected Proof

2009-11-05

Abstract: Owing to their high volatile aroma, the dried rhizomes of Cnidium officinale (C. officinale) and Ligusticum chuanxiong (L. chuanxiong) are used as herbal drugs to treat blood pressure depressant, a deficiency disease of antivitamin, inhibition of small intestine sympathetic nerve and as cosmetics for skin care. However, little has been known about the protective effect of their essential oils against ultraviolet B (UVB)-induced DNA damage. In this study, we report antioxidant activity of their essential oils using DPPH and ABTS scavenging assay. In addition, the composition of essential oils was measured by GC/MS. We also investigated whether these essential oils could inhibit UVB-induced DNA damage and apoptosis in the mammalian cell using intracellular DNA migration and expression level of phospho-H2A.X. Twenty constituents in the essential oil were identified and they showed good antioxidant properties, in that IC50 value in DPPH and ABTS showed 6.79 and 7.33μg/ml and 1.58 and 1.58μg/ml in C. officinale and L. chuanxiong. Their treatment inhibited the migration of damaged DNA induced by UV-B; furthermore, they decreased p21 expression and increased cyclin D1 expression as apoptosis-regulatory genes. These results suggest that essential oils in C. officinale and L. chuanxiong may exert inhibitory effects on DNA damage and apoptosis induced by UVB through their high free radical scavenging ability.

Estrogenic activity of bovine milk high or low in equol using immature mouse uterotrophic responses and an estrogen receptor transactivation assay - Uncorrected Proof

2009-11-05

Abstract: Background: Cow's milk contain phytoestrogens especially equol depending on the composition of the feed ration. However, it is unknown whether milk differing in equol exhibits different estrogenicity in model systems and thereby potentially in humans as milk consumers. Methods: The estrogenicity of high and low equol milk (HEM and LEM, respectively) and purified equol was investigated in immature female mice including mRNA expression of six estrogen-sensitive genes in uterine tissue. Extracts of HEM and LEM were also tested for estrogenicity in vitro in an estrogen receptor (ER) reporter gene assay with MVLN. Results: The total content of phytoestrogens was approximately 10 times higher in HEM compared with LEM, but levels of endogenous milk estrone and 17β-estradiol were similar in the two milk types (503–566 and 60–64.6pg/ml, respectively). There was no difference in uterine weight between mice receiving LEM and HEM, and no difference from controls. Equol (50 times the concentration in HEM) was not uterotrophic. The ERβ mRNA expression was down-regulated in the uteri of HEM mice compared with LEM and controls, but there was no difference between milk types for any of the other genes. Extracts of HEM showed a higher estrogenicity than extracts of LEM in MVLN cells, and there was a dose-dependent increase in estrogenicity by equol. Conclusion: The higher in vitro estrogenicity of HEM was not reflected as a higher uterine weight in vivo although the down-regulation of ERβ in uterine tissue of HEM mice could suggest some estrogenic activity of HEM at the gene expression level.

Hospital-based prevalence and sensitivity of high-risk human papillomavirus in Thai urban population - Uncorrected Proof

2009-11-05

Abstract: Background: To study the prevalence of high-risk human papillomavirus (HPV) types 16, 18, 31 and 33 in healthy Thai women using polymerase chain reaction (PCR) technique. Material and method: Two hundred and sixty three healthy urban women in Pathumthani, Thailand were recruited. Cervical cancer screening was performed and residual specimen from Pap smears was subjected to PCR to identify the presence of HPV types 16, 18, 31 and 33. Individuals’ demographic, health-specific and sexual behavior data were also collected. Results: Colposcopic biopsy revealed cases with high-grade squamous intraepithelial lesions (HSIL) and low-grade squamous intraepithelial lesions (LSIL). HPV 16 and 18 positive results were associated with abnormal Pap smears. Genotyping gave a 6.1%, 11.8%, 12.1%, and 14.1%, prevalence for HPV types 16, 18, 31 and 33, while 25% were infected with multiple HPV types. Discussion: High-risk HPV screening, used with abnormal pathology of HSIL gives 100% sensitivity and negative predictive value. Data from patient showed not significant correlation with neither different religion level of education, marital status, age of first sexual experience nor the number of sexual partners. Thus high-risk HPV screening is a recommended procedure with excellent sensitivity for detecting HSIL.

Remnant lipoproteins induced proliferation of human prostate cancer cell, PC-3 but not LNCaP, via low density lipoprotein receptor - Uncorrected Proof

2009-11-05

Abstract: Background: Hypertriglyceridemia has been shown to be one of the risk factors for prostate cancer. In this study, we investigated the effect of remnant lipoproteins on cell growth in prostate cancer cell lines. Methods: Remnant lipoproteins were isolated as remnant like particles (RLP) from human plasma. We used RLP for TG-rich lipoproteins and low density lipoproteins (LDL) for cholesterol-rich lipoproteins respectively and examined the effect of lipoproteins on proliferation of PC-3 and LNCaP cells using MTS assays. Moreover, we studied the effect of RLP and LDL treatment on the regulation of lipoprotein receptors in prostate cancer cells to investigate the relationship between lipoprotein-induced cell proliferation and lipoprotein receptor expression using real-time PCR, Western blotting assays and siRNA. Results: RLP effectively induced PC-3 cell proliferation more than LDL, whereas both RLP and LDL could not induce LNCaP cell proliferation except at a higher concentration of RLP. LDL receptor (LDLr) was expressed in both prostate cancer cells but there was a sharp difference of sterol regulation between two cells. In PC-3 cells, LDL decreased the LDLr expression in some degree, but RLP did not. Meanwhile LDLr expression in LNCaP was easily downregulated by RLP and LDL. Blocking LDLr function significantly inhibited both RLP- and LDL-induced PC-3 cell proliferation. Conclusions: This study demonstrated that RLP-induced PC-3 cell proliferation more than LDL; however, both RLP and LDL hardly induced LNCaP cell proliferation. The differences of proliferation by lipoproteins might be involved in the regulation of LDLr expression.

Overweight in relation to tumour size and axillary lymph node involvement in postmenopausal breast cancer patients—Differences between women invited to vs. not invited to mammography in a randomized screening trial - Uncorrected Proof

Åsa Olsson, Jens Peter Garne, Ingrid Tengrup, Sophia Zackrisson, Jonas Manjer — 2009-11-05

Abstract: Objectives: Overweight is associated with advanced stage at diagnosis in breast cancer patients. This could be explained by specific tumour characteristics or tumour promoting factors in the obese, but a diagnostic delay could also be of importance. Mammographic screening has caused a change towards diagnosis of less advanced tumours. This study investigates invitation to mammographic screening and the association between overweight and tumour size/axillary lymph node involvement at breast cancer diagnosis in postmenopausal women. Methods: In 1976 a randomized mammographic screening trial, inviting 50% of all women aged 45–69 was set up in Malmö, Sweden. The present analysis examined overweight (body mass index ≥25) as a determinant for large tumours (>20mm) and axillary lymph node involvement in postmenopausal women. These associations were studied separately in patients diagnosed prior to the mammographic screening trial, in invited women and in non-invited subjects (controls). In all, 2478 postmenopausal women were diagnosed with invasive breast cancer in these groups between 1961 and 1991. Logistic regression analysis allowed adjustment for other potential determinants of tumours size and axillary lymph node involvement. Results: In women diagnosed before the onset of the screening trial and in women not invited to mammography in the trial (controls), overweight was positively associated with large tumour size and axillary node involvement. There was no statistically significant association between overweight and these factors in women invited to mammographic screening. Conclusion: Invitation to mammographic screening may be particularly important for overweight postmenopausal women in order to detect breast tumours early.

Circulating antibodies directed against “polycyclic aromatic hydrocarbon-like” structures in the sera of cancer patients - Uncorrected Proof

Olivier Pouns, Arturo Mangas, Rafael Coveñas, Michel Geffard — 2009-11-05

Abstract: Background: An increase in immunoglobulin (Ig) A isotype directed against benzo(a)pyrene (BP) structure has previously been described in sera of cancer patients. In this study, new polycyclic aromatic hydrocarbon (PAH) conjugates were synthesized in order to more closely mimic the endogenous ligands of the cytosolic aryl hydrocarbon receptor (AhR). PAH [benzo(a)pyrene; 1,2-benzanthracene; dibenz[a,c]anthracene; 7,12-dimethylbenza[a]anthracene; benzo(ghi)perylene] were bound to protein carriers such as bovine serum albumin (BSA) via N-acetyl-cysteine (NAC). Methods: The levels of circulating antibodies (Abs) directed against PAH–NAC conjugates in the sera of cancer patients were evaluated using an Enzyme-Linked Immunosorbent Assay (ELISA) with these new conjugates. The avidity (IC50) and specificity of these circulating Abs were assessed via competition experiments. Results: An increase in Ig directed against these PAH–NAC conjugates was found in the sera of cancer patients, irrespective of the state and stage of the tumors. These Ig were principally of the A isotype. Sera from cancer patients had significantly higher optical density (OD) ranges than the controls, p<0.0001. The ELISA test for breast cancer (n=155) and ovarian cancer (n=62) identified 82% and 92% of positive patients, respectively. The percentage positive in the control group (n=60) was around 5%. Moreover, competition experiments with the different PAH–NAC conjugates and NAC–BSA revealed an estimated avidity of 10−6M for the circulating IgA antibodies. Conclusions: The Abs discriminated between the different PAH–NAC conjugates and NAC–BSA. Therefore, these Abs recognize a carcinogenic PAH–NAC structure and not only a BP structure. These markers may be useful in the future for monitoring cancer evolution and recurrence.

A polymorphic variant of the insulin-like growth factor type I receptor gene modifies risk of obesity for esophageal adenocarcinoma - Uncorrected Proof

2009-11-05

Abstract: Background: To investigate potential biologic mechanisms underlying the association between obesity and risk for esophageal adenocarcinoma (EADC), we studied the frequency of a common polymorphism of the insulin-like growth factor I receptor (IGF-IR) gene in patients with either gastroesophageal reflux disease (GERD), premalignant Barrett esophagus (BE) and or invasive EADC.Methods: Using a well characterized series of 431 individuals enrolled in a case–control study, we studied the frequency of the IGF-IR gene polymorphism, G1013A.Results: On multivariate analysis controlling for age and gender, in comparison to asymptomatic controls, obese individuals with the polymorphic A-variant (G/A, A/A) were found to have significantly increased risk for EADC (OR 4.81; 95%CI 1.09–21.15), whereas obese individuals with the G/G variant were not at statistically significant increased risk (OR 2.69; 95%CI 0.41–17.62). Similarly, compared to asymptomatic controls, only obese individuals with the A-variant (G/A, A/A) were at increased risk for BE (OR 3.11; 95%CI 1.12–8.63), while obese individuals with the G/G variant were not at increased risk for BE (OR 2.91; 95%CI 0.69–12.15).Conclusion: We conclude that the common IGF-IR gene polymorphism G1013A modulates the risk of obesity for EADC, an effect most likely mediated by altered the receptor function by influencing gene transcription or mRNA stability. These findings further implicate the insulin-like growth factor axis in the molecular pathogenesis of EADC, and represent a plausible mechanistic link underlying the association between obesity and malignancy.

A mini-review of familial ovarian germ cell tumors: An additional manifestation of the familial testicular germ cell tumor syndrome - Uncorrected Proof

Claudia Giambartolomei, Christine M. Mueller, Mark H. Greene, Larissa A. Korde — 2009-11-05

Abstract: Introduction While testicular germ cell tumors (TGCTs) are the most common malignancy in young men, germ cell tumors in women are uncommon. Familial clustering, epidemiologic evidence of increased risk with family or personal history of TGCT, and associations with genitourinary tract anomalies suggest an underlying genetic predisposition to TGCT, but traditional linkage studies have yet to identify a highly penetrant TGCT cancer susceptibility gene. In this paper, we investigate the familial occurrence of testicular and ovarian germ cell tumors. Methods We report a family in which a TGCT and an ovarian germ cell tumor (OGCT) occurred in two siblings, summarize the existing literature on familial occurrences of OGCT, either alone or in combination with extragonadal or TGCTs, and compare the incidence of familial and sporadic testicular and ovarian GCTs. Sporadic GCT data were obtained from the US Surveillance Epidemiology and End Results (SEER) registry. Results We identified 16 reports of OGCT occurring in conjunction with either ovarian, testicular or extragonadal GCT. In these familial cases, the mean age at onset of female dysgerminoma was younger than that noted in the general population (age 17 vs. age 24, p=0.01). In SEER, the incidence of TGCT was 15 times higher than that of OGCT. Histologic distributions in males and females showed distinctly different patterns. Discussion Although the incidence of OGCTs in the general population is quite low, its occurrence in multiple members of the same family and in families with TGCT suggests that a gene conferring susceptibility to GCTs may exist in some families.

MDM2, P53, P21WAF1 and pAKT protein levels in genesis and behaviour of adenoid cystic carcinoma - Uncorrected Proof

2009-11-05

Abstract: Background: MDM2, P53, P21WAF1 and pAKT are proteins associated with the balance between cell death and survival. There are many hypotheses regarding the role of these proteins in salivary gland tumours. However, many molecular events that activate or inactivate regulatory genes remain unknown. The aim of this study was to evaluate and to correlate MDM2, P53, P21WAF1 and pAKT protein expressions in adenoid cystic carcinomas (ACC). Methods: Twenty-two cases of ACC were evaluated by immunohistochemistry and one cell line derived from ACC was analyzed by Western Blotting and immunofluorescence techniques. Results: Strong MDM2 and pAKT, variable P53 and null P21 expressions were found in the cases analyzed, but no statistical correlation was established when comparing MDM2 and pAKT expressions in the 3 different ACC subtypes. The ACC cell line showed intense nuclear and cytoplasmatic MDM2 and pAKT expressions and null P53 and P21 expressions. Conclusions: Results indicate that MDM2 and pAKT are related to the tumorigenesis of ACC, but they might not be directly connected to tumour progression. We also demonstrate that the pAKT pathway is active in ACC and it seems to be activating the MDM2 shuttle from the cytoplasm to the nucleus, where it phosphorylates P53 and carries it to the cytoplasm for degradation.

Prepubertal octylphenol exposure up-regulate BRCA1 expression, down-regulate ERα expression and reduce rat mammary tumorigenesis - Uncorrected Proof

Jun-Hua Peng, Feng Zhang, Hua-Xing Zhang, Hong-Yan Fan — 2009-11-05

Abstract: Background: Endogenous estrogens play an important role in the development of breast cancer. Octylphenol (OP) and genistein (GEN) are estrogen-like chemicals. Prepubertal estradiol and genistein exposure can up-regulate BRCA1 mRNA in mammary gland and reduce futuer breast cancer risk. In the present study, the effects of prepubertal exposure to high-dose OP and GEN on mammary carcinogenesis and the association with the expression of BRCA1 and ERα were investigated. Methods: Prepubertal female Sprague–Dawley rats were exposed to 20, 40, 80mg/kg OP daily from postnatal day (PND) 22–28, subsequently, the rats were given a single dose of 100mg/kg 7,12-dimethylbenz [a] anthracene (DMBA) on PND42 to induce mammary tumor. Results: The incidence of DMBA-induced mammary tumors significantly decreased when rats were treated with 40mg/kg OP. BRCA1 mRNA and protein expression were found up-regulated and ERα expression was down-regulated in the mammary tumor when rats were exposed to 40mg/kg octylphenol. Conclusion: Exposure 40mg/kg octylphenol can reduce later breast cancer risk in prepubertal Sprague–Dawley rats, the protective effect of OP is associated with persistent up-regulation of BRCA1 and down-regulation of ERα in the mammary tumor.

Detection of p16 promotor hypermethylation in “Maras powder” and tobacco users - Uncorrected Proof

2009-11-05

Abstract: Background: A plant powder called “Maras powder” is widely used instead of cigarette smoking in the South-Eastern region of Turkey. It has been confirmed that this powder comprises tobacco Nicotiana rustica L. Methods: The aim of this study was to assess the effect of Maras powder and cigarette smoking on the P16 promotor hypermethylation. Twenty-two Maras powder users (Group I), 12 cigarette smokers (Group II), and 16 healthy controls who neither smoked nor used Maras powder (Group III) were included in the study. Hypermethylation of the P16 gene was examined using methylation-specific PCR (MSP) method in the blood of the three groups. Results: Aberrant P16 methylation was found in 7 of the 22 (31.8%) in Group I, in 3 of 12 (25%) in Group II, and in 1 of 16 (6.25%) in Group III. Conclusion: Maras powder may be as harmful as cigarette smoking, leading to hypermethylation in P16 and warrants detailed studies on this subject.

A gene marker panel covering the Wnt and the Ras-Raf-MEK-MAPK signalling pathways allows to detect gene mutations in 80% of early (UICC I) colon cancer stages in humans - Uncorrected Proof

2009-11-05

Abstract: Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243–1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80% of early stage CRC (UICC stages I and II) and over 90% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80–90% of human sporadic CRC samples analyzed.

Immunohistochemical analysis of selected molecular markers in esophagus precancerous, adenocarcinoma and squamous cell carcinoma in Iranian subjects - Uncorrected Proof

2009-11-05

Abstract: Background: The molecular and cellular mechanisms linking chronic inflammation and gastrointestinal malignancy are not known with certainty. Aim: To investigate changes in potential causative factors during progression of esophagus cancer in a population living in high-risk area in Iran. Subjects: Formalin-fixed, paraffin-embedded esophageal specimens (n=87) from patients with gastroesophageal reflux disease (GERD), Barrett's metaplasia, adenocarcinoma (ADC) and squamous cells carcinoma (SCC) were collected based on their pathological diagnosis. Methods: Immunohistochemical (IHC) technique was used to study tissue accumulation of P53, P21, cyclooxygenase-2 (COX-2), glutathione S-transferase-P (GST-Pi) and nitrotyrosine (NT) in patients and controls. Results: P53 expression was not detected in esophageal tissues from normal and GERD samples, whereas it was found positive in Barrett's, ADC, and SCC samples. P21 positive sample was relatively higher in ADC patients as compared to that in SCC (ADC: 52.6%; SCC: 25%). GST-Pi expression was equally accumulated in all the samples. NT was predominantly expressed in ADC (72.7%). COX-2 expression was significantly higher in Barrett's (60.0%) and ADC (66.6%) as compared to that in GERD, SCC and normal. These data were further confirmed by detecting the scores of immunostainings in all the positive samples. Conclusion: The pathological changes in ADC and SCC samples which was associated with increasing frequency of NT and COX-2 provides further evidence for involvement of these inflammatory factors in progression of esophagus cancer.

Human papillomavirus in oral leukoplakia is no prognostic indicator of malignant transformation - Uncorrected Proof

Shih-Wei Yang, Yun-Shien Lee, Tai-An Chen, Chang-Jer Wu, Chi-Neu Tsai — 2009-11-05

Abstract: Background: Oral leukoplakia is considered as a premalignant lesion for the development of oral squamous cell carcinoma (OSCC); several risks factors have been reported to contribute to this step-wise carcinogenesis; including human papillomavirus (HPV). Nevertheless, few reports have analyzed both the HPV status and the genotype in a single individual who develops OSCC from pre-existing oral leukoplakia. In this study, we surveyed the HPV status, genotype and clinicopathological risk factors in cases of malignant transformation from pre-existing oral leukoplakia. Methods: HPV genomic DNA was detected by PCR (MY09/MY11 in conjugation with nested primer-GP05+/GP06+) from paraffin sections, and the genotype was determined by direct DNA sequencing. Fisher's exact test and logistic regression were used to analyze risk factors for malignant transformation of oral cavity leukoplakia. Results: One hundred and sixty-seven patients with oral leukoplakia were enrolled; including 12 who had malignant transformation from the pre-existing oral leukoplakia. HPV prevalence was 22.8% in cases with oral leukoplakia. The risk factor associated with malignant transformation was recurrence of leukoplakia after treatment (p=0.03), nevertheless, HPV status was not statistically significant by logistic regression analysis. Among these 12 patients with malignant transformation from pre-existing oral leukoplakia, the status or genotype of HPV was chaotic; the oral habits of these patients might contribute to malignant transformation. Conclusions: Our data suggest that HPV in oral leukoplakia is no prognostic indicator of malignant transformation.

Overexpression of the IFN regulatory factor 4-binding protein in human colorectal cancer and its clinical significance - Uncorrected Proof

2009-11-05

Abstract: Background: IFN regulatory factor 4-binding protein (IBP) is a novel type of activator of Rho GTPases. It has been linked with differentiation and apoptosis of lymphocytes, but its function in oncogenesis remains unclear. Here we studied the expression of endogenous IBP in four human colorectal cancer cell lines, normal, adenoma and tumor colorectal tissues. Methods: Molecular (Western blot and RT-PCR), and confocal analyses were used to investigate IBP expression in human colorectal cancer cell lines. Matched normal and tumor tissue sections of 63 patients and 15 adenoma tissue sections were analyzed for IBP expression by immunohistochemistry (IHC). Results: IBP was ubiquitely expressed in human colorectal cancer cell lines. The expression of IBP can be detected at both the mRNA and protein level in SW480, SW620 and HT29 cells. Clinically, IBP were elevated in human colorectal cancer specimens in comparison to normal colorectal tissues. Substantial high expression of IBP was observed in colorectal cancer tissues (67%), whereas corresponding normal tissues and 15 adenoma tissues showed consistently absent immunoreactivity of IBP. Moreover, IBP expression is correlated with the differentiation level of colorectal cancer cells (p<0.05) and clinical stage of patients (p<0.01). Conclusions: Our data show, for the first time, a dysregulated expression of IBP in human colorectal cancer, offering new perspectives for its role in cancer development and progression. IBP may be a novel tumor marker and a therapeutic target for colorectal cancer.

G-308A TNF-α polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case-control study - Uncorrected Proof

2009-11-05

Abstract: Background: Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-α gene at position −308 promoter region is involved in the regulation of expression level and has been found to be associated with susceptibility to various types of cancer. Methods: To determine the association of the TNF-α gene G-308A polymorphism on the risk of hepatocellular carcinoma (HCC) in a Turkish population, a hospital-based case-control study was designed consisting of 110 diagnosis subjects with hepatocellular carcinoma and 110 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. Results: The distribution G-308A genotype was significantly associated with the risk of HCC (p<0.001, odds ratio [OR]=4.75, 95% confidence interval [CI]=2.25–9.82 for −308 AA/GA genotypes versus GG genotype). Conclusion: We suggested that the presence of the high producer allele −308A in the TNF-α gene appears to be associated with an increased risk for the development of HCC in Turkish population.

Natural history of esophageal and gastric cardia precursor by repetitive endoscope screening with 425 adults in a high-risk area in China - Uncorrected Proof

2009-11-05

Abstract: Objective: To observe the natural history and to determine appropriate screening interval for esophageal and gastric cardia precursors. Methods: Repetitive endoscopic screenings were performed among 425 forty to sixty-nine-year-old subjects in a high-risk region in Northern China. Results: We observed 8 subjects develop severe dysplasia (SD), another 8 develop carcinomas in situ (Cis), and 4 develop invasive cancer. The time and baseline diagnosis (BD) for the 8 SD subjects were: 13 months after normal epithelium in one case, 7 months after base cell hyperplasia (BCH) in another case, 3, 4, 4, and 10.5 months after mild dysplasia (mD) in four cases, and 12.5 and 43.4 months after moderate dysplasia (MD) in two cases. The time and BD for the 8 Cis cases were: 18 and 51.7 months after BCH in two cases, 48 months after mD in one case, 4 and 13 months after MD in two cases, and 3.5, 9, and 17.5 months after SD in the other three cases. The time and BD for the four invasive cancer cases were, 13 months after mD in one case, 50 months after MD in another case, and 14 and 19 months after SD in two cases. In addition to natural history observation, we also found sex, age (over 50 vs under 50), family history of upper gastrointestinal cancer, and the presence of multiple esophageal lugol-void lesions to be significant predicators for dysplastic progression; the corresponding OR (95% CI) and P-value were 1.98 (1.14–3.46) and 0.02; 2.32 (1.29–4.19) and 0.004; 1.81 (1.06–3.11) and 0.03; and 4.67 (2.70–8.06) and 0.000 respectively. Conclusions: A 5-year screening interval for BCH and mD, and a 3-year interval for MD, as suggested in China in 2005, may be too long for rapid developing precursors or individuals at high-risk for dysplastic progression. Therefore, shorter intervals should be considered.

Apoptosis and cell cycle arrest of human colorectal cancer cell line HT-29 induced by vanillin - Uncorrected Proof

KetLi Ho, Latifah Saiful Yazan, Norsharina Ismail, Maznah Ismail — 2009-11-05

Abstract: Background: Vanillin is responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies showed that vanillin could enhance the repair of mutations and thus function as an anti-mutagen. However, its role in cancer, a disease that is closely related to mutation has not yet been fully elucidated. Methods: Hence, this study investigated the cytolytic and cytostatic properties of vanillin against HT-29, a human colorectal cancer cell line. Methods used including cell viability assay, acridine orange (AO)–ethidium bromide (EB) double staining cell morphological analysis, Cell cycle analysis, annexin V–propidium iodide apoptosis test and 5-bromo-2-deoxyuridine (BrdU)-labeling cell proliferation assay. Results: Results showed that apoptosis was induced by vanillin and the IC50 for HT-29 and NIH/3T3 normal cell lines were 400μg/ml and 1000μg/ml, respectively. Different concentrations of vanillin arrest cell cycle at different checkpoints. 5-Bromo-2-deoxyuridine-labeling cell proliferation assay showed that G0/G1 arrest was achieved at lower concentration of vanillin (200μg/ml) while cell cycle analysis by flow cytometer showed that G2/M arrest occurs at higher concentration of vanillin (1000μg/ml). Conclusion: Cytolytic and cytostatic effects shown by vanillin showed that it could be a useful colorectal cancer preventive agent. Further in vivo study should be carried out to confirm that similar effects could happen in animals.

Clinical characteristics of tumors derived from colorectal cancer patients who harbor the TNFα-1031T/T and NOD2 3020insC polymorphism - Uncorrected Proof

2009-11-05

Abstract: Background: Genetic predispositions to disease have focused on highly penetrant causative changes in tumor suppressor genes or genes associated with DNA mismatch repair. New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization. Methods: In this report we have examined the tumor characteristics in a group of patients who have been shown to harbor two polymorphisms in two genes that are associated with the immune system NOD2 and TNFα. Results: Colorectal cancers from patients with NOD2 3020insC and TNFα-1031T/T constitutional changes are mostly right-sided disease (OR=2.21, p=0.03) with a tendency to higher stages (OR=2.41, p=0.06), increased number of associated polyps (OR=1.77, p=0.16) and later age of average age of disease onset (p=0.039). Conclusion: The results reveal that there appear to be specific characteristics associated with the tumors that may aid in determining management strategies to reduce the risk of disease.

Survivin and its spliced isoform gene expression is associated with proliferation of renal cancer cells and clinical stage of renal cancer - Uncorrected Proof

Keigo Okamura, Hidekazu Koike, Yoshitaka Sekine, Hiroshi Matsui, Kazuhiro Suzuki — 2009-11-05

Abstract: Background: Survivin has been implicated in inhibition of apoptosis. To date, alternatively spliced isoforms, Survivin-2α, -2B, -ΔEx3, -3B, have been described. We assessed the effect of survivin gene expression on the proliferation of renal cancer (RCC) cells, and studied the association of survivin and its spliced isoform gene expression levels with the clinical stage of RCC. Methods: Gene expression of survivin and its spliced isoform in RCC cells, Caki-1, were performed by RT-PCR. We knocked down the gene expression of Survivin using small interfering RNA (siRNA), and assessed the cell proliferation by MTS assay. Next, we quantified the gene expression levels of survivin and its isoform in nephrectomy samples using quantitative real-time PCR. Results: In Caki-1 cells, survivin and survivin-2α, -2B were expressed higher than survivin-ΔEx3. Decrease of Survivin gene expression by transfection of siRNA was accompanied by inhibition of the proliferation of Caki-1 cell with 36% decrease in comparison with negative control transfected cells (p<0.01). In clinical RCC tissues, survivin expression levels in metastatic stage were significantly higher compared with those in distant metastasis stage (M0:M1=1:4.81, p=0.014); survivin 2B gene expression levels in pT3 tumors were associated significantly higher than those in pT1 (pT1:pT3=1:4.50, p=0.043). No significant differences were found in survivin-2α expression levels and the ratio of surviving-2B/survivin gene expression levels among any clinical stages. Conclusion: We first demonstrated the gene expression of surviving-2α in renal cancer cells, and also showed that survivin and its spliced isoforms had associations with renal cancer cell proliferation and distant metastases.

Vitamin D receptor variants and the malignant melanoma risk: A population-based study - Uncorrected Proof

2009-11-05

Abstract: We sought to examine the association between four vitamin D receptor (VDR) common variants (rs1544410, rs731236, rs10735810, and rs4516035) and the risk of melanoma in the Polish population. We also determined the prevalence of compound carriers of VDR and known MM genetic risk factors MC1R and CDKN2A (A148T) variants. We examined 763 unselected melanoma cases, 763 healthy adults matched for sex and age with the melanoma cases and 777 newborns. None of the VDR variants alone or as compound carriers of two or more of the VDR genotypes were associated with MM risk. There were no major differences between the prevalences of the examined variants among patients with MM on UV-exposed and UV-non-exposed skin areas, as well as among early-onset and late-onset cases. We found no association between VDR and MC1R or between VDR and CDKN2A common variants. A statistically significant over-representation of one VDR haplotype: rs731236_A+rs1544410_T (OR=3.2, p=0.02) was detected. Linkage disequilibrium of rs1544410 and rs731236 was confirmed. To answer the question, whether VDR can be regarded as melanoma susceptibility gene, additional, large multi-center association studies have to be performed.

An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations - Uncorrected Proof

2009-11-05

Abstract: Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC). We specifically addressed anticipation in phenotypic HNPCC families in which no disease-predisposing mismatch repair (MMR) defect had been identified since risk estimates and age at onset are particularly difficult to determine in this cohort. The national Danish HNPCC register was used to identify families who fulfilled the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent–child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated an effect from anticipation with cancer diagnosed mean 11.4 years (t-test, p<0.0001) and mean 5.9 (bivariate model, p=0.02) years earlier in children than in parents. This observation suggests that anticipation may apply also to families without identified mutations and serves as a reminder to initiate surveillance programmes at young age also in HNPCC families with undefined genetic causes.

Long-term risk of receiving a total hip replacement in cancer patients - Uncorrected Proof

Eva Dybvik, Ove Furnes, Sophie D. Fosså, Clement Trovik, Stein Atle Lie — 2009-11-05

Abstract: To investigate whether cancer patients have an increased risk of receiving a total hip replacement compared to the standard population of Norway. By linking of The Cancer Register of Norway and The Norwegian Arthroplasty Register we obtained information on cancer diagnoses (type, date of diagnosis), total hip arthroplasties and date of death for all patients living in Norway. This includes 741,901 patients categorized into three groups: 652,197 patients with at least one cancer diagnosis but no hip arthroplasties, 72,469 patients with at least one hip arthroplasty but no cancer diagnosis and 17,235 patients who have at least one cancer diagnosis and at least one hip arthroplasty. Within this latter group, 8,586 individuals had been diagnosed with cancer prior to a total hip arthroplasty. Statistical methods applied in this study were Cox interval censored regression models and standardized incidence ratios (SIR). Cancer patients had a slightly increased risk of receiving a total hip arthroplasty compared to the Norwegian population (SIR=1.15 (95% CI, 1.12–1.17)). For primary tumours located cranially to the pelvic area there was no significant increase in risk for hip arthroplasty. An exception was breast cancer (SIR=1.13 (95% CI 1.08–1.18)). Cancer located in the pelvic region (SIR=1.20 (95% CI 1.16–1.24)), malignant lymphoma (SIR=1.30 (95% CI 1.15–1.46)) and leukaemia (SIR=1.17 (95% CI 1.01–1.34)) had an increased risk for receiving a total hip arthroplasty. Cancer survivors, mainly those with pelvic and lympho-hematological malignancies, have a small statistically significant increase in risk for receiving total hip arthroplasty.

Patterns of HER2 testing in the management of primary breast cancer - Uncorrected Proof

Mellisa Pensa, Helen Swede, Jessica A. Brockmeyer, David I. Gregorio — 2009-11-05

Abstract: Background: Women with invasive breast cancer should be tested for human epidermal growth factor receptor-2 (HER2) status at the time of diagnosis. To date, no population-based patterns of use studies have examined demographic and clinicopathologic factors associated with decisions by clinicians to test patients. Methods: We reviewed summary pathology reports submitted to the Connecticut Tumor Registry for all Black/African American (B/AA) women (n=644) and a 7% random sample (n=720) of White women diagnosed in 2000–2003 with primary invasive breast carcinoma. Receipt of a HER2 test (yes vs. no) was examined in relation to patient race, age, socioeconomic status, year of diagnosis, estrogen receptor (ER) status, tumor grade, lymph node status, size and stage at diagnosis. Results: A greater proportion of tumors from B/AA patients were tested compared to those of White women (69.5% vs. 61.9%, p<0.05). Tumors of patients under the age of 60 were 1.50-times more likely than older women to have been tested, and B/AA women were 1.40-times more likely than White patients to be tested. HER2 testing was more likely to be observed when information also was reported about ER status (OR=15.9, p<0.001), tumor grade (OR=2.28, p<0.05), tumor size (OR=2.16, p<0.05), and lymph node status (OR=2.06, p<0.05). Conclusions: Variation in which breast cancer patients received HER2 testing appears to reflect expectations about a woman's prognosis. Discrepancies in receipt of testing deserve further study as current guidelines call for all tumors to be assessed in order to adequately characterize prognosis and determine eligibility for HER2-targeted therapy.

Absence of PIWIL2 (HILI) expression in human bladder cancer cell lines and tissues - Uncorrected Proof

2009-11-05

Abstract: Background: PIWIL2, a member of Argonaute family of proteins, is exclusively expressed in testis and functions in development and maintenance of germline stem cells. Recently, ectopic expression of PIWIL2 has been reported in a variety of human and mouse tumors. To investigate a potential involvement of PIWIL2 in human bladder cancer, we examined its expression in several human bladder cancer cell lines, normal uroepithelial cell cultures, and some bladder tissues. Methods: Relative expression of PIWIL2 was determined by real-time quantitative RT-PCR in fifteen bladder carcinoma cell lines, six normal uroepithelial cell cultures and seventy tissue specimens of tumor, tumor margins and morphologically normal tissues of bladder. Specific primers for PIWIL2, TBP and GAPDH (as two internal controls) were used for reverse transcription polymerase chain reaction technique. Results: Real-time qRT-PCR demonstrated high PIWIL2 expression in testis tissue, but at least 240-fold lower expression in all examined cell lines. The highest expression outside testis was observed in one of six primary cultures of normal uroepithelial cells, but even lower expression of PIWIL2 was detected in any of the examined tumor and non-tumor tissues. Conclusion: Lack of PIWIL2 expression in most tissues along with its aberrant expression in some tumors candidate the gene as an attractive tumor marker for some neoplasms. However, our study indicates that PIWIL2 does not play a role in carcinogenesis of human bladder carcinoma.

Education and cancer incidence in a rural population in south India - Uncorrected Proof

2009-11-05

Abstract: Background: Population-based studies describing the association between education and cancer incidence has not yet been reported from India. Methods: Information on the educational attainment of 4417 cancer cases aged 14 years and above, diagnosed during 2003–2006 in Dindigul district, Tamil Nadu, India, was obtained from the Dindigul Ambilikkai Cancer Registry, which registers invasive cancer cases by active methods from 102 data sources. Population distribution by 5-year age groups and for four educational levels namely no education, education ≤5 years, 6–12 years and >12 years, was obtained from census data. Standardized rate ratios based on age-standardized rates were calculated to study cancer risks for different educational levels. Results: Men and women with no education had higher overall cancer incidence rates compared to the educated population. The risk of cervix, mouth, esophagus, stomach and lung cancers were inversely associated with higher levels of education whereas a high incidence of breast cancer was observed with increasing educational levels. The standardized rate ratio of cervical cancer 0.32 (95% CI: 0.19–0.52) and of breast cancer was 6.08 (95% CI: 1.81–20.48) for women with more than 12 years of education compared to those with no education. There was paucity of cases in the highest education level for most cancers. Conclusion: With more and more women in rural India becoming educated, one could foresee breast cancer becoming more frequent even in rural areas of India in future.

Cancer mortality and occupational exposure to aromatic amines and inhalable aerosols in rubber tire manufacturing in Poland - Uncorrected Proof

2009-11-05

Abstract: Aim: Most data on carcinogenic risk in the rubber industry are based on data from Western countries. This study assessed cancer risks in a retrospective cohort in a Polish tire manufacturing plant, relying on quantified exposure to inhalable aerosols and aromatic amines instead of job titles or external comparisons. Methods: Cumulative exposure for all exposures was assigned to cohort members based on estimates from a company-specific JEM. Cancer risks associated with cumulative exposure adjusted for co-exposures, gender and year of birth were calculated. Results: Exposure levels were higher for women than for men. Aromatic amine exposure was significantly associated with increased urinary bladder cancer risk (RR=7.32–8.27), depending on exposure level, and prostate cancer at low levels only (RR=5.86). In women, increased risks were found for all cancers (RR=2.50) and of the digestive organs and peritoneum (RR=4.54) at low level only, while an exposure-response association with breast cancer risk was found. Inhalable aerosol exposure was associated with cancers of the liver and intrahepatic bile ducts in a dose-dependent manner, while dose-dependent reduced risks were found for respiratory cancers (most notably the larynx) and cancer of the colon. Conclusions: Increased risks for specific cancer sites in this rubber plant were similar to Western Europe and the US. However, several cancer risks were gender-specific which could relate to higher exposure levels in women or to differences in exposures to chemicals not assessed in this study.

Novel generating protective SNP barcode for breast cancer using particle swarm optimization - Uncorrected Proof

Cheng-Hong Yang, Hsueh-Wei Chang, Yu-Huei Cheng, Li-Yeh Chuang — 2009-11-05

Abstract: Background: High-throughput single nucleotide polymorphism (SNP) genotyping generates a huge amount of SNP data in genome-wide association studies. Simultaneous analyses for multiple SNP interactions associated with many diseases and cancers are essential; however, these analyses are still computationally challenging. Methods: In this study, we propose an odds ratio-based binary particle swarm optimization (OR-BPSO) method to evaluate the risk of breast cancer. Results: BPSO provides the combinational SNPs with their corresponding genotype, called SNP barcodes, with the maximal difference of occurrence between the control and breast cancer groups. A specific SNP barcode with an optimized fitness value was identified among seven SNP combinations within the space of one minute. The identified SNP barcodes with the best performance between control and breast cancer groups were found to be control-dominant, suggesting that these SNP barcodes may prove protective against breast cancer. After statistical analysis, these control-dominant SNP barcodes were processed for odds ratio analysis for quantitative measurement with regard to the risk of breast cancer. Conclusion: This study proposes an effective high-speed method to analyze the SNP–SNP interactions for breast cancer association study.

General practitioner and specialist views on colonoscopic screening of first-degree relatives of colorectal cancer patients - Uncorrected Proof

2009-11-05

Abstract: Introduction: : Barriers to targeted colonoscopic screening of first-degree relatives of colorectal cancer patients have been the subject of considerable literature, always as seen from the patient's viewpoint. In the specific context of screening individuals with a family history, physicians play a predominant role in motivating their colorectal cancer patients to pass on screening information to their relatives. The aim of this study was to examine the views of general practitioners and specialists regarding barriers and facilitators affecting participation of relatives in colonoscopic screening. Methods: A qualitative study was conducted to collect and analyse information from two focus groups of 4 general practitioners and 9 gastroenterologists respectively, and from semi-structured individual interviews with 10 general practitioners, 2 surgeons and 3 oncologists. An extended focus group of 36 gastroenterologists was organized to validate the results. Results: The main barriers to colonoscopic screening of FDRs were associated with lack of direct communication between physicians and FDRs. Physicians needed support in the task of informing index patients and persuading them to transfer information on screening to their FDRs. The general practitioners spoke of their expectations in terms of training in and motivation for promoting screening and the gastroenterologists expressed the wish for patient education material specific to colonoscopy and for systematic post-colonoscopy consultations to inform patients about their results, follow-up and screening their relatives. Conclusion: The findings, notably the need for specific education materials and for training to improve the motivation of physicians, will help to develop effective interventions intended to increase participation in screening.

Obesity is associated with atypia in breast ductal lavage of women with proliferative breast disease - Uncorrected Proof

2009-11-05

Abstract: Background: Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. Methods: We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. Results: There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index was also significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Conclusions: Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk.