Cancer Epidemiology

Editorial Board

2012-06-01

The descriptive epidemiology of female breast cancer: An international comparison of screening, incidence, survival and mortality

2012-03-14

Abstract: Background: This paper presents the latest international descriptive epidemiological data for invasive breast cancer amongst women, including incidence, survival and mortality, as well as information on mammographic screening programmes.Results: Almost 1.4 million women were diagnosed with breast cancer worldwide in 2008 and approximately 459,000 deaths were recorded. Incidence rates were much higher in more developed countries compared to less developed countries (71.7/100,000 and 29.3/100,000 respectively, adjusted to the World 2000 Standard Population) whereas the corresponding mortality rates were 17.1/100,000 and 11.8/100,000. Five-year relative survival estimates range from 12% in parts of Africa to almost 90% in the United States, Australia and Canada, with the differential linked to a combination of early detection, access to treatment services and cultural barriers. Observed improvements in breast cancer survival in more developed parts of the world over recent decades have been attributed to the introduction of population-based screening using mammography and the systemic use of adjuvant therapies.Conclusion: The future worldwide breast cancer burden will be strongly influenced by large predicted rises in incidence throughout parts of Asia due to an increasingly “westernised” lifestyle. Efforts are underway to reduce the global disparities in survival for women with breast cancer using cost-effective interventions.

Breast cancer among Yemeni women using the National Oncology Centre Registry 2004–2010

S. El-Zaemey, N. Nagi, L. Fritschi, J. Heyworth — 2012-02-13

Abstract: Background: In developing countries including Arab countries breast cancer is one of the most common cancers found in women. Even though breast cancer incidence is lower in Arab developing countries than in western countries, Arabic women are more likely to be diagnosed at an earlier age than the women in western countries. Method: A descriptive study was undertaken to investigate the type of breast cancer, lymph node involvement, side of breast and, region and age distribution of breast cancer patients registered in the National Oncology Centre in Yemen. Results: From September 2004 to December 2010, 2654 women across Yemen diagnosed with breast cancer were registered in the National Oncology Centre for treatment. Between the years 2004 and 2010, breast cancer represented 22% of all cancers registered in women. Seventy-one per cent of the women were aged 50 or younger at the time of diagnosis. The most common age group affected was women aged 41–50 years, with (35%) of cases occurring in this age. Invasive ductal carcinoma was the most common pathology (76%) and 79% of the patients had lymph node involvement at the time of diagnosis. Approximately 2% had bilateral disease and the frequency of left (44%) and right breast cancer (42%) were similar. Conclusion: This study has shown that breast cancer is a disease of young women in Yemen. The majority of women presented with lymph node involvement. Hence efforts are needed to increase breast cancer awareness in Yemen for early detection at all age groups, and to target women living in areas that have lower access to health care services.

Gender-specific spatio-temporal patterns of colorectal cancer incidence in Navarre, Spain (1990–2005)

M.D. Ugarte, J. Etxeberria, T. Goicoa, E. Ardanaz — 2011-10-31

Abstract: Introduction: In the last ten to twenty years, a stabilization or decline in colorectal cancer (CRC) incidence has been observed in some countries across the world but not in Spain. Our objective here is to assess the gender-specific CRC spatio-temporal pattern in the health areas of Navarre, a Spanish province, during the period 1990–2005. Methods: For each gender, a model with spatio-temporal CAR (Conditional Autoregressive) distributions is used for smoothing the incidence risks. Smoothing is carried out in two dimensions: space and time, allowing for a different time evolution in each health area. An estimated incidence trend curve for each health area and the corresponding confidence bands are obtained. To analyze the evolution of the geographical patterns of CRC incidence risks, maps are also provided. Results: In both genders, CRC shows an increasing trend in most of the areas. In the second half of the period 1998–2005 most of the areas have risks above one although not all statistically significant. In general females present equal or lower risks than males in all areas during the studied period. Conclusions: Colorectal cancer incidence risk is still increasing in the health areas of Navarre. Promoting healthful lifestyles for primary prevention and early detection programs could help to reverse the trend in the province.

High prevalence of cervical squamous intraepithelial lesions in women on antiretroviral therapy in Cameroon: Is targeted screening feasible?

2011-10-24

Abstract: Background: Cervical cancer is the most common cancer in women in low-income countries. Although cervical cancer incidence and mortality is higher in HIV-positive women, resource limitations restrict the implementation of systematic screening programs in these women. We explored the potential for targeted screening by assessing the prevalence, severity and predictors of cervical squamous intra-epithelial lesions (SILs) in HIV-positive women in Cameroon. Methods and findings: We conducted a cross-sectional study of women on antiretroviral therapy in Cameroon. Socio-demographic, behavioral, and clinical information was obtained from eligible women. Cervical exfoliated cells were then collected, a conventional cytology performed and epithelial lesions classified according to the Bethesda 2001 system. A total of 282 women, aged 19–68 years, were enrolled in this study. The median CD4 count was 179 cells/microliter (interquartile range: 100–271). SILs were detected in 43.5% of the 276 women with satisfactory samples: including atypical squamous cells of unknown significance (ASCUS) 0.7%, low-grade SIL (LSIL) 25.0%, atypical squamous cells, cannot exclude high grade lesions (ASC-H) 14.5%, and high-grade SIL (HSIL) 3.3%. None of the demographic or clinical characteristics considered significantly predicted the presence of any SILs or the presence of severe lesions requiring colposcopy. Conclusion: The prevalence of SIL in women on antiretroviral therapy in Cameroon was high underscoring the need for screening and care in this population. In the absence of any accurate demographic or clinical predictor of SIL, targeted screening does not seem feasible. Alternative affordable screening options need to be explored.

Different effects of multiple health status indicators on breast and colorectal cancer screening in a nationally representative US sample

Anjali D. Deshpande, Amy McQueen, Elliot J. Coups — 2011-10-24

Abstract: Objective: To examine the independent associations between multiple health status indicators and breast and colorectal cancer screening (CRCS) in a national US sample. Study design and setting: Analysis of cross-sectional data from the 2005 National Health Interview Survey (NHIS) involved 5115 men and 7100 women aged 50 years and older. Measures: Health status indicators included: self-reported perceived health status, number of chronic conditions, and functional limitation due to a chronic condition. Individuals were considered adherent to CRCS guidelines if they reported having a home-based fecal occult blood test in the past year or endoscopy in the past 10 years. Women were adherent to breast cancer screening guidelines if they reported having a mammogram in the previous 2 years. Statistical analyses were conducted using SUDAAN software to account for the complex sampling of the NHIS survey. Logistic regression was used to examine associations between each of the health status indicators and screening adherence for CRCS and mammography and to calculate estimated screening rates. Results: The three health status indicators were independently and differentially associated with screening adherence. Poor perceived health was associated with lower mammography among women, whereas a greater number of chronic conditions were consistently associated with greater screening. In adjusted analyses, functional limitation was only significantly associated with greater CRCS among women. Conclusions: Our analyses included three common indicators of health status and provide new evidence of their complex associations with cancer screening. Future studies must examine the mechanisms by which these indicators influence screening recommendations and adherence among older adults over time.

Associations between CYP1A1 and CYP2E1 polymorphisms and susceptibility to esophageal cancer in Chaoshan and Taihang areas of China

Dianliang Wang, Min Su, Dongping Tian, Shuang Liang, Jing Zhang — 2011-11-03

Abstract: Purpose: To study the causes of esophageal cancer in Chaoshan and Taihang areas. Methods: By using gel-based DNA microarray genotyping method, four cancer-related polymorphisms including CYP1A1 m2, CYP1A1 m4, CYP2E1 Pst I and CYP2E1 Rsa I were studied with 565 (CYP1A1) or 482 (CYP2E1) cases and 468 (CYP1A1) or 466 (CYP2E1) controls. Results: For CYP1A1 m2, the mutant allele frequencies were 21.3% (Chaoshan) and 19.6% (Taihang), and OR for AG versus AA genotype (Chaoshan) was 1.855 (95% CI [1.227–2.805]). For CYP1A1 m4, no mutant allele was detectable. For CYP2E1 Pst I, the mutant allele frequencies were 27.3% (Chaoshan) and 29.4% (Taihang), and OR for GG versus CC genotype (Taihang) was 3.263 (95% CI [1.059–10.052]). For CYP2E1 Rsa I, the mutant allele frequencies were 27.3% (Chaoshan) and 29.6% (Taihang), and OR for CC versus TT genotype (Taihang) was 3.167 (95% CI [1.026–9.776]). Conclusion: The results suggest that AG genotype of CYP1A1 in Chaoshan area and GG (CC) genotype of CYP2E1 in Taihang area are significantly associated with esophageal cancer susceptibility.

Polymorphisms of TREH, IL4R and CCDC26 genes associated with risk of glioma

2012-02-16

Abstract: Introduction: Glioma is one of the most aggressive human tumors; however, little is known about its genetic risk factors. The role of heredity is likely to be explained by combinations of common low-risk variants. Previous studies have indicated that more than 100 single nucleotide polymorphisms (SNPs) are associated with the risk of glioma. Methods: To further investigate how and to what extent these SNPs contribute to glioma susceptibility in a Chinese population, we analyzed 43 SNPs of 226 glioma patients and 254 normal people in order to evaluate the associations between SNPs and the risk of glioma. Results: Overall, we found three protective alleles for glioma in patients: the allele “G” of rs1801275 in the IL4R gene by allele model (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.50–0.99; P=0.04) and dominant model (OR, 0.67; 95% CI, 0.46–0.99; P=0.04) analysis respectively, the allele “T” of rs17748 in the TREH gene by recessive model (OR, 0.48; 95% CI, 0.23–1.01; P=0.05) analysis, and the allele “G” of rs6470745 in CCDC26 gene by recessive model (OR, 0.48; 95% CI, 0.26–0.89; P=0.02) analysis. Conclusion: This study provides evidence for three glioma susceptibility genes – TREH, IL4R and CCDC26 – in a Chinese population; this may shed light on molecular markers of glioma susceptibility and could therefore be used as a diagnostic and prognostic marker for glioma patients in clinical study.

Frequent low expression of chromatin remodeling gene ARID1A in breast cancer and its clinical significance

2011-08-18

Abstract: Background: ARID1A gene encodes BAF250a which is a member of the ARID family of DNA-binding proteins and a subunit of human SWI/SNF-related complexes. Low expression of ARID1A has been correlated with specific tumor cell lines or specific pathological types of cancer tissue. The purpose of this study was to investigate the expression of ARID1A in invasive ductal breast carcinomas and to evaluate its clinicopathological characteristics and prognostic value. Methods: ARID1A mRNA expression was evaluated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 40 pairs of fresh frozen breast cancer and normal breast samples. BAF250a expression was evaluated by immunohistochemistry in 112 paraffin-embedded surgical specimens of invasive breast cancers and 20 cases of matched normal breast tissues. We further analyzed the clinicopathological characteristics of ARID1A expression. Overall survival time was assessed by the Kaplan–Meier method and Cox regression model. Results: ARID1A mRNA expression was lower in breast cancer tissue than in corresponding normal tissue (P<0.001), and this decreased expression level was markedly associated with factors such as larger tumor size (P=0.038), higher stage (P=0.016), ER(−) (P=0.038), higher Ki-67 (P=0.025), P53 mutation (P=0.018) and ER(−)/PR(−)/Her-2(−) molecular subtype (P=0.044). With immunohistochemical staining, we showed that low BAF250a expression existed in 56% (63/112) of the breast cancers tissues. Low BAF250a expression was significantly associated with tumor stage (P=0.021), P53 (P=0.018), Ki-67 (P=0.031) and ER(−)/PR(−)/Her-2(−) molecular subtype (P=0.044). Low ARID1A expression was a predictor, not an independent, of overall survival. Conclusion: These data suggest that low ARID1A expression is frequent in breast cancers, and we need to investigate further the role of ARID1A and SWI/SNF complexes in breast tumorigenesis, especially in triple-negative breast cancer.

Family history of non-hematologic cancers among Waldenstrom macroglobulinemia patients: A preliminary study

2011-11-09

Abstract: Background: Little is known about the epidemiology and etiology of Waldenstrom macroglobulinemia (WM). Despite several studies of the relation between family history and B-cell disorders and WM, family history of non-hematologic cancers has not been systematically investigated. We thus examined associations of family history of breast, colorectal, lung, ovarian, and prostate cancers with WM.Methods: All probands aged 20–79 years with bone marrow biopsy-confirmed diagnosis of WM between May 1, 1999 and January 1, 2010 at the Bing Center for Waldenstrom Macroglobulinemia were eligible for inclusion in our analysis. We reviewed medical records for eligible probands to determine family history of cancer (defined as a cancer diagnosis for ≥1 first-degree relative(s) of the proband). Using expected values constructed from the United States National Health Interview Survey, we estimated age- and race-standardized rate ratios (RRs) for family history of breast, colorectal, lung, ovarian, and prostate cancers by WM subtype.Results: Family history of prostate cancer had the largest overall rate ratio (RR=1.4, 95% confidence limits [CL]: 1.1, 1.7), and among sporadic cases, family history of prostate and breast cancer had the largest rate ratios (prostate: RR=1.3, 95% CL: 1.1, 1.7; breast: RR=1.3, 95% CL: 1.2, 1.6).Conclusion: Our study suggests that it may be worthwhile to pursue these associations in a case–control study with uniform selection and data collection for cases and controls, and at least some record-based information on family history.

Will vaccinated women attend cervical screening? A population based survey of human papillomavirus vaccination and cervical screening among young women in Victoria, Australia

Julia M.L. Brotherton, Robyn M. Mullins — 2011-12-08

Abstract: Objectives: To assess human papillomavirus (HPV) vaccination coverage and attitudes to vaccination and Pap screening in young women. Design: Population-based telephone survey. Setting: Victoria, Australia. Participants: 234 women resident in Victoria aged 18–28 years in May 2009. Main outcome measures: Self-reported HPV vaccination uptake, reasons for non-receipt or failure to complete vaccination, knowledge and attitudes about HPV vaccination and Pap screening, and cervical screening intentions. Results: The response rate for eligible households was 62.4%. Half of the women (56%, n=131) had previously had a Pap test and 74% (age standardised estimate) had received HPV vaccine. Of the vaccinated women, 5% had received one dose only, 18% two doses and 76% had completed the course (1.7% unsure of number of doses). Vaccination uptake was highest in the youngest women (declining from 90% for at least one dose in women aged 18–38.5% in women aged 28; p for trend <0.001). Among women who had heard of the vaccine, 96% knew Pap tests were still needed after it, although 20% thought the vaccine could prevent all cervical cancers and 9% thought the vaccine could treat cervical abnormalities and cancer. Among vaccinated women, 8% of women agreed that having been vaccinated made them less likely to have Pap tests in the future. Conclusions: Self-reported coverage in this sample was higher than that recorded on the national vaccination register. Young women report the message that Pap tests are required after vaccination, but there are gaps in their knowledge about the limitations of the vaccine so it remains to be seen if they actually follow through with having Pap tests. Ongoing monitoring of cervical screening rates will be important as this cohort ages.

Value and prognostic significance of mitotic rate in a retrospective series of pT1 cutaneous malignant melanoma patients

G. Ponti, A. Pollio, A.M. Cesinaro, G. Pellacani, C. Magnoni, S. Seidenari — 2011-11-28

Abstract: Introduction: Patients affected by thin melanomas (≤1mm) generally have a good prognosis; however, some have a recurrence and eventually die of the disease. The seventh edition of the American Joint Committee on Cancer (AJCC) melanoma staging system, introduced mitotic rate (MR) as one of the primary criteria for staging thin melanoma. Materials and methods In this study, we sought to determine the prognostic value of mitotic rate in a retrospective cohort of localized primary cutaneous melanoma patients. Results: In total, 286 cases of pT1 primary malignant melanoma occurring in the period 2003–2008 were evaluated. Mitotic counts were re-assessed on standard sections of cases without mitosis and with at least 1 mitosis at diagnosis; 5-year follow-up and recurrence-free survival were available for all patients. Of the 56 radically treated pT1b melanoma patients, 4 (7.1%) had recurrent disease. These data support the efficacy of the incorporation of mitogenicity into AJCC staging for localized cutaneous melanoma and indicate the difficulties in the accuracy and reproducibility of the mitotic count system.

The importance of exposure rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium

2012-03-27

Abstract: Background: Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. Methods: The authors pooled data from 12 case–control studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. Results: For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01). Conclusions: Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases.

Near infrared spectroscopy combined with least squares support vector machines and fuzzy rule-building expert system applied to diagnosis of endometrial carcinoma

Fan Yang, Jing Tian, Yuhong Xiang, Zhuoyong Zhang, Peter de B. Harrington — 2011-11-04

Abstract: Objective: The feasibility of early diagnosis of endometrial carcinoma was studied by least squares support vector machines (LS-SVM) and fuzzy rule-building expert system (FuRES) that classified near infrared (NIR) spectra of tissues. Methods: NIR spectra of 77 specimens of endometrium were collected. The spectra were pretreated by principal component orthogonal signal correction (PC-OSC) and direct orthogonal signal correction (DOSC) methods to improve the signal-to-noise ratio (SNR) and remove the influences of background and baseline. The effects of modeling parameters were investigated using bootstrapped Latin-partition methods. Results: The optimal LS-SVM model of the PC-OSC pretreatment method successfully classified the samples with prediction accuracies of 96.8±1.4%. Conclusions: The proposed procedure proved to be rapid and convenient, which is suitable to be developed as a non-invasive diagnosis method for cancer tissue.

Changing epidemiology of two male predominant cancers

Nan Li, Xueming Wang, Junshan Zhai, Lijun Jiang, Yuefan Zhang — 2012-02-13

Analyzing the time trends of disease rates can help understand the etiology of the disease since a changing trend implies the changes of environmental risk factors while a constant trend may be explained by some genetic or stable environmental risk factors. Describing the gender difference in disease rates also has important etiological implications on risk factors with different distributions in males and females. As an integration of these two methodologies, Dyego Leandro Bezerra de Souza and colleagues provided a good example of presenting the changing epidemiology of two male predominant cancers, laryngeal and hypopharyngeal cancers, in Spain . In this recently published paper, the authors found that the gap between genders in these two cancers has been narrowed in recent years and concluded that the observed trends might be explained by the different changes in tobacco and alcohol consumptions between genders.

2012-02-23

Analyzing the time trends of disease rates can help understand the etiology of the disease since a changing trend implies the changes of environmental risk factors while a constant trend may be explained by some genetic or stable environmental risk factors. Describing the gender difference in disease rates also has important etiological implications on risk factors with different distributions in males and females. As an integration of these two methodologies, Dyego Leandro Bezerra de Souza and colleagues provided a good example of presenting the changing epidemiology of two male predominant cancers, laryngeal and hypopharyngeal cancers, in Spain . In this recently published paper, the authors found the gap between genders in these two cancers has been narrowed in recent years and concluded that the observed trends might be explained by the different changes in tobacco and alcohol consumptions between genders.

Erratum to “Perinatal risk factors for childhood testicular germ-cell cancer: A Nordic population-based study”

2011-12-09

The Publisher regrets that an error occurred in the conclusion of the abstract. The last sentence should read: “Our findings support the notion that abnormal fetal growth rate confers a risk in pediatric testicular cancer.”

Lack of association between p53 codon 72 polymorphism and endometrial cancer: A meta-analysis

Wenru Tang, Xinggang He, Ying Chan, Ying Luo — 2012-01-18

Abstract: Background: It has been suggested that the p53 tumor suppressor gene Arg72Pro polymorphism is associated with endometrial cancer. However, results have been inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and endometrial cancer. Methods: An electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and the association was assessed by pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Nine published studies, including 829 endometrial cancer cases and 1387 controls, were identified. The overall results suggested that the variant genotypes were not associated with the endometrial cancer risk in all genetic models (additive model: OR 1.027, 95% CI 0.893–1.18, P=0.71; recessive model: OR 1.099, 95% CI 0.802–1.507, P=0.556; dominant model: OR 1.013, 95% CI 0.842–1.219 P=0.89). Similarly, the results were negative in subgroup analyses for ethnicity (Caucasian, Asian). Conclusion: This meta-analysis suggests that p53 codon 72 polymorphism is not associated with increased risk of endometrial cancer, especially in Caucasians and Asians. To validate the association between this polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed.

Incidence patterns of small bowel cancer in a population-based study in Sweden: Increase in duodenal adenocarcinoma

Yunxia Lu, Robin Fröbom, Jesper Lagergren — 2012-02-15

Abstract: Background: Increasing incidences of malignant small bowel tumours have been reported, but data from European populations are limited. This study aimed to clarify the incidence patterns of malignant small bowel tumours in Sweden.Methods: Patients with a first and primary malignant small bowel tumour were identified from the Swedish Cancer Register during the study period 1960–2009. Sex-specific and age-standardised incidence rates of these tumours were calculated by their anatomical location and histological type in different time periods. Figures were plotted to show the proportions and incidence rates over time, and joinpoint loglinear regression models were estimated to assess any time trends.Results: A total of 6604 patients with malignant small bowel tumours were identified. The age-standardised incidence of all malignant small bowel tumours increased from 14.2 to 19.7 per 1,000,000 person-years during the study period. The incidence of duodenal cancer increased more than 3-fold (from 1.6 to 5.4 per 1,000,000 person-years), which was mainly expained by a dramatical rising trend of adenocarcinoma of the duodenum (from 0.7 to 4.2 per 1,000,000 person-years). Malignant tumours of small bowel with unspecified anatomical locations showed a slight increase (from 7.0 to 7.9 per 1,000,000). The incidence of small bowel tumours in other locations or of other histological types was more stable.Conclusions: The incidence of small bowel malignancies has increased during the period 1960–2009. Among the specific types of small bowel cancer, a particularly rapid increase was found for duodenal adenocarcinoma.

Socioeconomic inequalities in incidence of lung and upper aero-digestive tract cancer by age, tumour subtype and sex: A population-based study in Scotland (2000–2007)

2012-03-05

Abstract: Background: Lung and upper aero-digestive tract (UADT) cancer risk is associated with socioeconomic inequality (SEI) but the degree of socioeconomic burden by age, tumour subtype, and sex is not known.Methods: We reviewed 216,305 cases excluding non melanoma skin cancer (All Cancer) comprising 37,274 lung; 8216 head and neck; and 6534 oesophageal cancers from 2000 to 2007 classified into anatomical or morphology subtypes. Deprivation was measured using the Scottish Index of Multiple Deprivation and SEI was measured using the Slope Index of Inequality and the Relative Index of Inequality (RII). Analyses were partitioned by 5-year age group and sex. RII was adapted to rank tumour type contribution to All Cancer SEI and to examine subtype by age and sex simultaneously. Rank was defined as proportion of All Cancer SEI.Results: All Cancer SEI was greater for males (RII=0.366; female RII=0.279); the combination of lung and UADT SEI contributed 91% and 81% respectively to All Cancer SEI. For both sexes lung and UADT subtypes showed significant SEI (P<0.001) except oesophageal adenocarcinoma in males (P=0.193); for females, SEI was borderline significant (P=0.048). Although RII rank differed by sex, all lung and larynx subtypes contributed most to All Cancer SEI with RII rank for oral cavity, oesophagus-squamous cell, and oropharynx following. For males 40–44 years, SEI increased abruptly peaking at 55–59 years. For females, SEI gradually peaked 10 years later. In both sexes, the SEI peak preceded peak incidence.Conclusion: SEI in lung and UADT cancers vary greatly by age, tumour subtype and sex; these variations are likely to largely reflect differences between the sexes in risk behaviours which vary by birth cohort and are socioeconomically patterned.

Polymorphisms in MSH2 gene and risk of gastric cancer, and interactions with lifestyle factors in a Chinese population

2012-02-22

Abstract: Background: Although polymorphisms in DNA mismatch repair (MMR) gene MSH2 have been associated with risks of many cancers, little is known about their etiology role in gastric cancer (GC) and the potential interacting role with lifestyle factors known to damage DNA. Methods: A population-based study was conducted in 3 counties (Jintan, Taixing and Huaian) of Jiangsu Province, the high-risk areas of GC in China. We investigated the association of polymorphisms IVS12−6T>C and IVS10+12G>A in MSH2 gene with the risk of GC and the potential gene–lifestyle interaction. Results: The risk of GC was found to be associated with the IVS12−6C allele (CC vs TT, OR=2.34, 95% CI: 1.17–4.71) and IVS10+12A allele (GA or AA vs GG, OR=1.55, 95% CI: 1.14–2.21; and GA vs GG, OR=1.51, 95% CI: 1.04–2.17). Stratified analysis indicated that an increased risk of GC also was observed in: suspected familial subjects carrying the IVS12−6T>C (OR=1.68, 95% CI: 1.27–2.66) or IVS10+12G>A (OR=2.57, 95% CI: 1.53–4.10); or younger subjects carrying the IVS12−6T>C (OR=2.15, 95% CI: 1.24–3.91) or IVS10+12G>A (OR=2.23, 95% CI: 1.20–4.33); or male subjects carrying the IVS10+12G>A (OR=1.64; 95% CI: 1.10–2.54). Furthermore, the combined IVS12−6CC and IVS10+12AA genotypes also significantly increased the risk of GC (OR=2.12, 95% CI: 1.22–3.66). Statistically significant interactions were observed between: IVS10+12G>A and drinking, high pickled food or fried food intake (OR=2.32; 95% CI: 1.43–3.78, OR=2.55; 95% CI: 1.48–4.21 and OR=2.88; 95% CI: 1.70–4.94, respectively); and IVS12−6T>C and high pickled food intake or fried food intake (OR=2.65; 95% CI: 1.62–4.47 and OR=2.48; 95% CI: 1.42–4.13, respectively). Conclusion: The IVS10+12G>A and IVS12−6T>C polymorphisms in MSH2 gene appear to be associated with risk of GC in this Chinese population. Risk for GC, stratified by related genotypes, was further modified by drinking, high pickled food or fried food intake. Larger prospective studies are needed to confirm these findings.

BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic breast cancer and controls

2012-02-20

Abstract: Objective Epigenetics, particularly DNA methylation, has recently been shown to be important in breast cancer initiation. We investigated the clinical and prognostic importance of whole blood breast cancer early onset gene 1 (BRCA1) DNA methylation in sporadic breast cancer. Methods Genomic DNA was extracted from the peripheral blood cells (PBCs) of 902 breast cancer patients at diagnosis, with no BRCA1 mutation, and 990 control women. DNA methylation was measured by quantitative analysis of methylated alleles (QAMA) to estimate the extent of methylation of 2 CpG sites in the promoter region of BRCA1 oncosuppressor. Results BRCA1 promoter methylation rate in PBCs was 47.1% with a 95% confidence interval [46.1; 48.1] in breast cancer patients, and 45.9% with a 95% confidence interval [45.0; 46.8] in controls. We found a trend toward BRCA1 promoter hypermethylation in PBCs of sporadic breast cancer patients compared with controls. Association between methylation and clinicopathological features was evaluated using statistical tests. BRCA1 promoter methylation in PBCs increased significantly in breast cancer patients compared with controls, for age over 70 years (p=0.022), in post-menopausal status (p=0.013), for a body mass index (BMI) <20 (p=0.0095) or a waist-to-hip ratio (WHR) ≤76.8 (p=0.0027). We also found an association of increased BRCA1 promoter methylation in PBCs with ACA/ACA genotype for the SNP Thr594Thr in ESR (estrogen receptor gene), known to be associated with breast cancer risk (p=0.092), reflecting the reduced presence of this genotype in this breast cancer case-control study. Conclusion Analysis of site-specific DNA methylation in PBCs by QAMA provides quantitative DNA methylation values that may serve as important prognostic indicators.

Behavioral and sociodemographic risk factors for serological and DNA evidence of HPV6, 11, 16, 18 infections

2012-01-09

Abstract: Introduction: Risk for HPV6/11/16/18 infections in young sexually active, behaviorally low-risk females is not well described and may inform public policy. Methods: To assess exposure risk for HPV/6/11/16/18 among 16–23 year old low-risk females, data for 2409 female clinical trial participants were evaluated. Baseline visit self-reported sexual, behavioral and demographic characteristics; and results from HPV genotyping and serology, and other clinical laboratory assays were analyzed. All subjects reported <5 lifetime male sexual partners and no prior abnormal cytology at baseline. Results: While 98% (2211/2255) were naïve to HPV16 or 18 and 99.6% (2246/2255) were naïve for 1–3 index HPVs, 27% (616/2255) showed antibody, DNA or both for ≥1 index HPV. While 18% (409/2255) tested HPV16- or -18-antibody- or -DNA-positive, only 2% (44/2255) tested positive for both types. Against this high background, other sexually transmitted infections (STIs) were uncommonly detected, suggesting low sexual risk-taking behavior. The adjusted analyses showed race, age, alcohol consumption, current Chlamydia trachomatis (chlamydia) and Trichamonas vaginalis (trichomoniasis), bacterial vaginosis (BV), number of lifetime male sex partners predicted positive index-HPV antibody test results. However, only the number of male sex partners predicted positivity for HPV6/11- and 16/18-DNA, and chlamydia infection predicted positivity for HPV6/11-DNA alone. Conclusions: Taken together, type-specific HPV-DNA and -antibody evidence of HPV6/11/16/18 infections among behaviorally low-risk 16–23 year old females is high. Since almost all participants would have benefited by either currently available bivalent or quadrivalent vaccine strategies, delaying vaccination beyond menarche may be a missed opportunity to fully protect young females against HPV6/11/16/18 infections and related dysplasias. Early diagnosis and treatment of chlamydia and trichomonas may be important in HPV pathogenesis.

What is the role of family in promoting faecal occult blood test screening? Exploring physician, average-risk individual, and family perceptions

2012-01-31

Abstract: Background: Although the number of Canadians being screened for colon cancer is rising, only 40% of Canadians aged 50 years or older reported they had engaged in faecal occult blood test (FOBT) screening as recommended. The notion of ‘partnerships’ that is inclusive of physicians, individuals at average-risk for colorectal cancer, and influential family members is receiving more attention in primary health care literature and policy on promoting health maintenance behaviours. To the best of our knowledge there are no studies that have taken a tripartite approach in describing perspectives of these three key stakeholders on the role of family in promoting adherence to FOBT. The aim of this study was to address the gap in understanding the perspectives of primary care physicians, individuals at average-risk for colorectal cancer, and family on family role in promoting adherence to FOBT screening. Method: We employed a qualitative design and conducted semi-structured interviews with 15 physicians, 27 patients at average-risk for colorectal cancer, and 19 family members or friends from urban and rural Manitoba, Canada between October 2008 and March 2010. Interviews were audio-recorded, transcribed verbatim, and analysed using content analysis and constant comparative techniques. Results: While physicians described a clear role for family in managing chronic disease or dealing with acute or serious illness, they identified barriers in working with family to promote FOBT screening: lack of time, privacy and confidentiality concerns, and family dynamics. Conversely, patients and family described instrumental, emotional, informational, and appraisal roles that family play in promoting FOBT outside medical encounters. Conclusion: Adherence to colorectal cancer screening is based on supportive ‘patient–physician’ dialogue that is separate from assistive ‘patient–family member’ relations. Further research is required to explore social support mechanisms involving family members outside medical encounters that hold promise in boosting self-efficacy, overcoming barriers, and gaining positive reinforcement for individuals at average-risk when making the decision to engage in FOBT.