Cancer Epidemiology

Editorial Board

2012-02-01

Africa's growing cancer burden: Environmental and occupational contributions

Valerie A. McCormack, Joachim Schüz — 2011-09-30

Highlights: ► Africa's cancer burden will at least double between 2008 and 2030. ► High levels of environmental/occupational carcinogenic exposures arise from difficulties to enforce health standards, use of out-dated machinery, lack of personal protective measures and of hazard knowledge. ► Exposure sources/settings include mining, pesticide-intensive agriculture, chemical industries, chrysotile asbestos use, hazardous wastes, air pollution. ► Unique exposure patterns provide research opportunities to clarify the role of possibly-carcinogenic agents. ► Regulation and surveillance of exposure levels and of cancer are needed for locally-tailored cancer control plans.Abstract: Background: Primary prevention measures are needed for Africa's cancer burden (715,000 new cases and 542,000 deaths in 2008), a burden projected to double by 2030 due to demographic changes alone. Control of cancer-causing infections and lifestyle-related carcinogens will play a significant role in prevention, but less often addressed are environmental and occupational contributions. Methods: We review environmental issues that contribute to Africa's Cancer burden. Results: We demonstrate evidence of the impact of environmental carcinogens on the cancer burden as of now and that circumstances present today may increase their contribution further. Suboptimal implementation and monitoring of environmental protection and of occupational health standards, including in the informal sector, use of outdated technologies in industry and lack of awareness of potential hazards in the specific employment structure give rise to high levels of exposures. Carcinogens of concern include (i) those that have been long present (e.g. indoor air pollution) whose contribution may increase as life-expectancy increases and long latency periods for cancer are realised, (ii) exposures in mining and agricultural sectors and (iii) modern environmental hazards, including urban air pollution and agents arising from the mis-management of hazardous waste from local, industrial and trans-boundary sources. Conclusions: Actions taken to reduce exposures and research to fill gaps in knowledge, adapted to local settings, could help mitigate the cancer burden.

Time trends and age–period–cohort analyses on incidence rates of nasopharyngeal carcinoma during 1993–2007 in Wuhan, China

2011-07-29

Abstract: Background: Declines in incidence rates of nasopharyngeal carcinoma (NPC) were observed in Hong Kong and Taiwan but not other high-risk regions in China, while evidences from low-risk regions in China are still lacking. This study aimed to examine the time trends (1993–2007) of NPC in Wuhan (a low-risk region) and assess the birth cohort and calendar period effects on the observed temporal trends. Method: Using data from Wuhan Cancer Registry, age-standardized annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (2000) as the reference. Trend in incidence rates of NPC during 1993–2007 was evaluated. Age–period–cohort models were also applied to assess the effects of age, calendar time and birth cohort on the observed temporal trends. Results: A total of 1685 new NPC cases (1210 males and 475 females) were diagnosed during 1993–2007 in Wuhan. The annual percentage change in incidence rates of NPC were 0.15% (95% confidence interval: −3.88% to 4.34%) for males and −1.17% (95% confidence interval: −4.85% to 2.66%) for females. No obvious cohort or period effect on the incidence rates of NPC was observed. Conclusion: The incidence rates of NPC remained stable during 1993–2007 in Wuhan, a low-risk region in China.

Time trends in testicular cancer in Croatia 1983–2007: Rapid increases in incidence, no declines in mortality

Nino Sincic, Tomislav Kulis, Ariana Znaor, Freddie Bray — 2011-10-10

Abstract: Testicular cancer, although a rare malignancy, represents the most common cancer in young male populations of Western origin. While increasing incidence trends of testicular cancer have been reported, mortality is declining in many high-resource settings. Using national data from the Croatian National Cancer Registry for the period 1983–2007, time trends were analysed by joinpoint regression and Age–Period–Cohort models. The present study is the first to analyse the testicular cancer trends in the Croatian population. Over the 25-year period, a mean number of 89 incident cases and 13 deaths were reported annually. The observed mean annual increases in age-standardised rates were 7.0% for incidence and 1.6% for mortality, with no abrupt linear changes (joinpoints) identified. The incidence rates of testicular cancer incidence have been steeply increasing in successive cohorts born since the mid-1930s. The rapid rise in testicular cancer incidence in the Croatian population appears to be one of the highest rates of increase recorded in Europe and worldwide. The lack of decline in the mortality rates over time, while based on relatively few deaths, highlights a need for improvements in diagnostics and management of therapy in Croatia in order to improve the survival and quality-of-life of testicular cancer patients.

Comparison of methods for calculating relative survival in population-based studies

Mark J. Rutherford, Paul W. Dickman, Paul C. Lambert — 2011-06-02

Abstract: Background: It is vital that unbiased estimates of relative survival are estimated and reported by cancer registries. A single figure of relative survival is often required to make reporting simpler. This can be obtained by pooling all ages or, more commonly, by using age-standardisation. The various methods for providing a single figure estimate of relative survival can give very different estimates. Methods: The problem is illustrated through an example using Finnish thyroid cancer data. The differences are further explored through a simulation study that investigates the effect of age on the estimates of relative survival. Results: The example highlights that in practice the all-age estimates from the various methods can be substantially different (up to 6 percentage units at 15 years of follow-up). The simulation study confirms the finding that differing estimates for the all-age estimates of relative survival are obtained. Performing age-standardisation makes the methods more comparable and results in better estimation of the true net survival. Conclusions: The all-age estimates of relative survival rarely give an appropriate estimate of net survival. We feel that modelling or stratifying by age when calculating relative survival is vitally important as the lack of homogeneity in the cohort of patients leads to potentially biased estimates. We feel that the methods using modelling provide a greater flexibility than life-table based approaches. The flexible parametric approach does not require an arbitrary splitting of the time-scale, which makes it more computationally efficient. It also has the advantage of easily being extended to incorporate time-dependent effects.

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States

2011-08-08

Abstract: Background: Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This study's objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics. Methods: The state cancer registries of California, Colorado and Idaho provided linked cancer registry and death certificate data for individuals who died between 2002 and 2004, had at least one cancer listed on their death certificate and were diagnosed with cancer between 1993 and 2004. These linked data were used to calculate the site-specific proportion of cancers not selected as the UCD (non-UCD) among all cancer-related deaths (any mention on the death certificate). In addition, the retrospective concordance between the death certificate and the population-based cancer registry, measured as confirmations rates, was calculated for deaths with cancer as the UCD, as a non-UCD, and for any mention. Results: Overall, non-UCD deaths comprised 9.5 percent of total deaths; 11 of the 79 cancer sites had proportions greater than 3 standard deviations from 9.5 percent. The confirmation rates for UCD and for any mention did not differ significantly for any of the cancer sites. Conclusion and impact: The site-specific variation in proportions and rates suggests that for a few cancer sites, death rates might be computed for both UCD and any mention of the cancer site on the death certificate. Nevertheless, this study provides evidence that, in general, restricting to UCD deaths will not under report cancer mortality statistics.

Using method triangulation to validate a new instrument (CPWQ-com) assessing cancer patients’ satisfaction with communication

2011-09-19

Abstract: Purpose: Patients’ perceptions of care including the communication with health care staff is recognized as an important aspect of the quality of cancer care. Using mixed methods, we developed and validated a short instrument assessing this communication. Methods: Based on focus group interviews with 77 informants, an 8-item instrument was developed. This short instrument aimed at assessing overall aspects of the communication between cancer patients and health care staff. The items were validated first through cognitive interviews with patient–observer agreement with 52 cancer patients who completed the questions and then participated in tape-recorded open-ended interviews. Observer ratings of the interviews were compared with the patients’ written responses collected before interviews and kappa values were calculated. The comprehensibility of each item was subsequently elaborated in traditional cognitive interviews with 17 cancer patients. Finally, psychometric analyses took place with data from 1490 cancer patients. Results: The weighted kappas concerning patient–observer agreement ranged 0.31–0.88. Disagreements mainly consisted of the observer choosing the response category indicating the highest level of satisfaction whereas the patients had chosen the second highest level. Cognitive interviews showed that the questions were generally interpreted as intended. One item was excluded due to low validity. A sum scale of the remaining seven items had high reliability (Cronbach's alpha 0.89). Conclusions: Seven items performed well. They proved to be valid measures of satisfaction with communication with the health care staff and constitute a sum scale with high reliability. The cognitive interviews provided valuable insight into the patients’ perception of communication.

Comparison of racial differences in childhood cancer risk in case-control studies and population-based cancer registries

2011-05-25

Abstract: Introduction: Although selection bias in case-control studies has been studied extensively, little is known about selection of cases and controls among various ethnic groups. This study compares racial differences in childhood cancer rates as estimated by case-control studies with various design features. It also compares estimates of racial distribution among cases as reported by case-control studies to those observed for an ideal case series with complete ascertainment of cases for these studies or in population-based cancer registries in corresponding geographic regions and calendar periods. Methods: Peer-reviewed publications on childhood leukemia and brain tumors from North America, published between 1980 and 2007, were reviewed. Incidence data by race/ethnicity were compiled from research publications, federal cancer statistics, and cancer registries. Meta-analysis was conducted to assess racial/ethnic differences by study characteristics. Racial distributions of cases from published case-control studies were compared to those of a presumably noncensored case distribution (i.e. include both participating and non-participating cases in a case-control study) or cases recorded by cancer registries. Results: In interview-based case-control studies of childhood cancer, the proportion of Whites compared to non-Whites tended to be higher among controls than among cases; however, the opposite was true for record-based case-control studies. Additionally, the proportion of Whites tended to be higher among the participating cases in the published case-control studies compared to the proportion of Whites among the non-participating cases or in cancer registries. Conclusions: Investigators need to consider differential participation by racial group as a potential source of bias in the interpretation of case-control study results.

Family history of cancer and non-malignant diseases and risk of childhood acute lymphoblastic leukemia: A Children's Oncology Group Study

2011-07-15

Highlights: ► We analyzed the association of family history of cancer and non-malignant diseases in childhood acutelymphoblastic leukemia. ► We found a borderline association of ALL and having a family member with a history of cancer. ► Family history of food and drug allergies demonstrated a modestly reduced risk as did family history of rheumatoid arthritis. ► We found no associations with family history of any autoimmune diseases, immunodeficiencies, birth defects, thyroid diseases andrisk of childhood.Abstract: Background: Studies of family history of cancer and non-malignant diseases in childhood acute lymphoblastic leukemia (ALL) show inconsistent findings. Most studies show no increased risk with family history of cancer. Non-malignant diseases such as allergic diseases, autoimmune diseases, birth defects and thyroid diseases have been reported to be associated with ALL. Methods: We conducted a case-control study of family history of cancer and selected non-malignant conditions (allergic diseases, autoimmune diseases, birth defects, and thyroid diseases). ALL cases were obtained from Children's Cancer Group institutions from January 1989 to June 1993. Controls were recruited via random digit dialing. Family history for first degree relatives and grandparents of ALL cases and controls was collected by structured telephone questionnaires. Conditional logistical regression was used to calculate odds ratios adjusting for potential confounders. Results: We found a borderline association of ALL and having a family member with a history of cancer in cases (n=1842) compared to controls (n=1986) (OR=0.98, 95%CI=0.93, 1.00) and an inverse association for esophageal cancer based on small numbers. Family history of food and drug allergies demonstrated a modestly reduced risk (OR=0.83, 95%CI=0.73, 0.95) as did family history of rheumatoid arthritis (OR=0.79, 95%CI=0.65, 0.96). There were no associations with family history of any autoimmune diseases, immunodeficiencies, birth defects, thyroid diseases and risk of childhood ALL. Conclusions: These results show no association of overall family history of cancer with childhood ALL, while providing additional evidence for an inverse association with family history of allergic disease. Two potentially new associations of ALL with family history of esophageal cancer and rheumatoid arthritis require confirmation in other studies and validation with medical records.

Anthropometric factors, physical activity, and risk of Non-Hodgkin's lymphoma in the Women's Health Initiative

2011-06-10

Abstract: Background: Incidence rates of non-Hodgkin's lymphoma (NHL) increased substantially in the United States and worldwide during the latter part of the 20th century, but little is known about its etiology. Obesity is associated with impaired immune function through which it may influence the risk of NHL; other factors reflecting energy homeostasis (height, abdominal adiposity, and physical activity) may also be involved. Methods: We examined the association of anthropometric factors and physical activity with risk of NHL and its major subtypes in a large cohort of women aged 50–79 years old who were enrolled at 40 clinical centers in the United States between 1993 and 1998. Over a mean follow-up period of 11 years, 1123 cases of NHL were identified among 158,975 women. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Height at baseline was positively associated with risk of all NHL and with that of diffuse large B-cell lymphoma (HRsq4vs.q1 1.19, 95% CI 1.00–1.43 and 1.43, 95% CI 1.01–2.03, respectively). Measures of obesity and abdominal adiposity at baseline were not associated with risk. Hazard ratios for NHL were increased for women in the highest quartile of weight and body mass index at age 18 (HRsq4vs.q1 1.29, 95% CI 1.01–1.65 and 1.27, 95% CI 1.01–1.59, respectively). Some measures of recreational physical activity were modestly associated with increased risk of NHL overall, but there were no clear associations with specific subtypes. Conclusion: Our findings regarding anthropometric measures are consistent with those of several previous reports, suggesting that early life influences on growth and immune function may influence the risk of NHL later in life.

Main dietary compounds and pancreatic cancer risk. The quantitative analysis of case–control and cohort studies

Piotr Paluszkiewicz, Katarzyna Smolińska, Iwona Dębińska, Waldemar A. Turski — 2011-05-25

Abstract: Objective: Estimation of the role of main dietary compounds in the risk of developing pancreatic cancer. Research methods and procedures: Literature published till 2010 was reviewed and selected for further analysis. The used terms were: red meat, minced meat, ham, bacon, sausages, white meat, poultry, vegetables, fish, eggs, fruits, lifestyle, diet, pancreatic cancer and pancreatic neoplasm. The collected data were meta-analysed with calculation of combined relative risk and 95% confidence interval as well as studies heterogeneity. Results: A meta-analysis of 11 case–control studies indicates that red meat ingestion elevates pancreatic cancer risk by 48% (95% CI=1.25–1.76). The vegetables and fruit reduce the risk by 38% (95% CI=0.54–0.73) and 29% (95% CI=0.59–0.84), respectively. The pooled analyses of 10 cohort studies do not show significant relations between main dietary compound ingestion and pancreatic cancer risk. Conclusion: The red meat intake is associated with elevated risk of pancreatic cancer in contrast to vegetables and fruit ingestion. The ingestion of red meat, vegetables and fruit in cohort studies was not influenced on pancreatic cancer risk. The role of fish, poultry and eggs was not significant in both case–control and cohort studies, thus further studies were needed.

CYP1AI, glutathione S-transferase gene polymorphisms and risk of Polycythemia vera

Randa G. Naffa, Abdalla S. Awidi, Al-Motassem F. Yousef, Said I. Ismail — 2011-05-18

Abstract: Background: Associations between polymorphisms for gene encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the present study was to evaluate the association of polymorphisms of cytochrome P450 (CYP1A1) and GST deletions with the incidence of Polycythemia vera (PV) among the Jordanian population. Methods: The study included 61 PV patients and 70 cancer-free healthy controls. CYP1A1 (m1, m2, m3, m4) and GST (T1, M1) genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. The risk of cancer associated with gene polymorphisms was estimated by calculations of odds ratio (ORs) and confidence intervals (95% CIs) using Mantel–Haenszel statistics. Results: A statistically significant difference between the PV group and the control group was observed in the case of GSTM1 null genotype with 3.38 fold increase in risk of developing PV (95% CI=1.63–7.01, p=0.001) while GSTT1 null genotype showed no significance (OR=1.11; 95% CI=0.50–2.44, p=0.38). No significant association was found between the CYP1A1 mutant genotypes (m1, m2, m4) and PV. The m3 genotype was absent in both patients and controls. Interestingly, a substantial significant increase of PV risk for the combination of GSTM1 null genotype and CYP1A1 m1 (T6235C) genotype was observed (OR=4.38; 95% CI=1.15–16.73, p=.02). Furthermore, the present case–control study showed that the studied Jordanian population generally resembles Caucasian populations with respect to the frequencies of CYP1A1 polymorphisms. Conclusion: Our data suggests that GSTM1 null genotype alone and in combination with CYP1A1 m1 genotype may be predisposing risk factors for PV in the Jordanian population.

Detection of methylated tissue factor pathway inhibitor 2 and human long DNA in fecal samples of patients with colorectal cancer in China

2011-05-10

Abstract: Background: To investigate the feasibility of detecting methylated tissue factor pathway inhibitor (TFPI2) and quantifying human long DNA with fluorescent quantitative Alu PCR in fecal DNA as a non-invasive screening tool for colorectal cancer (CRC). Materials and Methods: Methylation-specific PCR (MSP) was performed to analyze TFPI2 gene promoter methylation status in a blinded fashion in stool samples taken from 30 endoscopically diagnosed healthy controls, 20 patients with adenomas, and 60 patients with colorectal cancer. Real-time Alu PCR was used to quantify human long DNA. Results: The specificity of fecal TFPI2 MSP assay and long DNA assay was 100% and 83.3%, respectively. The sensitivity of fecal TFPI2 MSP assay and long DNA assay was 68.3% and 53.3%, respectively. The sensitivity of fecal DNA assay (either marker being positive) was 86.7%, which was high for CRC. Conclusions: Our results have demonstrated the feasibility of using TFPI2 methylation and quantify human long DNA with fluorescent quantitative Alu PCR in fecal samples as a new noninvasive test for CRC.

Meta-analysis of cancer risk in folic acid supplementation trials

Joseph E. Baggott, Robert A. Oster, Tsunenobu Tamura — 2011-05-25

Abstract: Several reports suggest that folate has a procarcinogenic effect. Folate has a unique role because its coenzymes are needed for de novo purine and thymine nucleotide biosynthesis. Antifolates, such as methotrexate, are used in cancer treatment. Using a meta-analysis weighted for the duration of folic acid (pteroylglutamic acid) supplementation, we analyzed the cancer incidence of six previously published large prospective folic acid-supplementation trials in men and women. These articles were carefully selected from over 1100 identified using PubMed search. Our analyses suggest that cancer incidences were higher in the folic acid-supplemented groups than the non-folic acid-supplemented groups (relative risk=1.21 [95% confidence interval: 1.05–1.39]). Folic acid-supplementation trials should be performed with careful monitoring of cancer incidence. Solid monitoring systems to detect side effects, including increase in cancer risk, should be established before the initiation of folic acid supplementation trials.

Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system

2011-05-25

Abstract: Background: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Autoantibodies to tumor-associated proteins in the serum profile, as new biomarkers, may improve the early detection of HCC. Methods: In this study, we interrogated a HCC cDNA T7 phage library for tumor-associated proteins using biopan enrichment techniques with HCC patient and normal sera. The enrichment of tumor-associated proteins after biopanning was tested using plaque assay and immunochemical detection. The putative tumor-associated phage clones were collected for PCR and sequencing analysis. Identities of those selected sequences were revealed through the sequence BLAST program. The identified phage-expressed proteins were then used to develop phage protein ELISA to measure matching autoantibodies using 70 HCC patients, 50 chronic hepatitis patients, and 70 normal serum samples. The logistic regression model and leave-one-out validation were used to evaluate predictive accuracies with a single marker as well as with combined markers. Results: Twenty-six phage-displayed proteins have sequence identity with known or putative tumor-associated proteins. Immunochemical reactivity of patient sera with phage-expressed proteins showed that the autoantibodies to phage-expressed protein CENPF, DDX3, HSPA4, HSPA5, VIM, LMNB1, and TP53 had statistical significance in HCC patients. Measurements of the seven autoantibodies combined in a logistic regression model showed that combined measurements of these autoantibodies was more predictive of disease than any single antibody alone, underscoring the importance of identifying multiple potential markers. Conclusion: Autoantibody in the serum profiling is a promising approach for early detection and diagnosis of HCC. The panel of autoantibodies appears preferable to achieve superior accuracy rather than an autoantibody alone, and may have significant relevance to tumor biology, novel drug development, and immunotherapies.

Breast-conserving therapy versus modified radical mastectomy: Socioeconomic status determines who receives what—Results from case–control study in Tianjin, China

2011-05-09

Abstract: Background: Despite anecdotal evidence linking socioeconomic status and choices on surgical management in breast cancer patients in China, no scientific evaluations have ever been conducted. The objective of this study was to evaluate patient factors that influence patients’ treatment options between breast cancer patients receiving breast-conserving therapy (BCT) and modified radical mastectomy (MRM). Methods: A total of 268 stage I–II breast cancer patients treated with BCT in Tianjin Cancer Hospital, from January 2005 to January 2007, were compared with 200 randomly selected breast cancer patients (controls) treated with MRM. A personal health questionnaire (PHQ) was used to assess the factors that may affect the surgical decision making. Chi-squared test and multiple logistic regressions were used to examine factors associated with BCT. Results: BCT patients who were younger and were more likely to live in urban areas had medical insurance, higher levels of education and family income. Patients with medical insurance coverage were approximately six times more likely to receive BCT than patients without medical insurance after controlling for other potentially confounding factors. Similar results were also observed for family income. The observed differences cannot be explained by clinical aspects of their disease, such as tumor stage, estrogen receptor, and lymph node involvement. Conclusion: Breast cancer patients’ socioeconomic status, rather than their clinical condition, is the predominant factor in determining whether a breast cancer patient receives BCT or not. These results provide a snapshot on how socioeconomic status influences cancer care provision in China. Future efforts should be made towards reducing discrepancies in treatment options for cancer patients caused by social class and socioeconomic status.

Biochemical-markers for the diagnosis of bone metastasis: A clinical review

Qian Huang, Xuenong Ouyang — 2011-02-21

Abstract: The preferential metastasis of cancer cells to skeleton not only disrupts the process of bone remodeling and influences the therapeutic decision, but also results in severe complications. Although the current diagnosis of bone metastases (BM) relies on bone imaging techniques, they are not sensitive enough for early detection as well as they are invasive and expensive to use. Since factors derived from bone metabolism are potentially useful to diagnose metastatic bone disease in cancer patients, a number of clinical trials have been carried out on this area. Results suggest that higher levels of bone biomarkers are associated with an increased risk of BM. As a result, biochemical-markers are showing prospects in early diagnosis of BM. This review summarizes the available evidence on the clinical use of biochemical-markers in the diagnosis of various cancers with high incidence of BM including breast, prostate and lung.

Revisiting the association between alcohol drinking and oral cancer in nonsmoking and betel quid non-chewing individuals

Stefano Petti, Masood Mohd, Crispian Scully — 2011-10-10

Abstract: Background: Alcohol drinking is an oral cancer (OC) risk factor; tobacco smoking (TS) and betel quid chewing (BQC) are oral carcinogens and effect modifiers of drinking. Although the assessment of the independent effect of drinking on OC must necessarily account for effect modifiers, no observational study has included interaction terms between drinking, TS, BQC in regression analyses. In order to assess the independent association between drinking and OC, this pooled analysis focused on subjects who were not exposed to such effect modifiers. Methods: Case-control studies on OC, which discriminated non TS/non BQC drinkers from multiexposed drinkers were searched. Exposed subjects (≥1 drink daily, ≥10 years) were compared to unexposed subjects (non/occasional drinkers). Unadjusted odds ratios (ORs) were extracted/calculated. Pooled ORs were assessed with the random-effect method, which assumed high between-study heterogeneity (assessed with Cochran's Q). Robustness of estimates was investigated through use of adjusted ORs, correction for publication bias, sensitivity analysis to inclusion criteria. The drinking–TS interaction was assessed with the Interaction Contrast Ratio (ICR) and the Attributable Proportion due to Interaction (AP). Results: Sixteen studies were used, with substantially high heterogeneity. The pooled OR was 0.787 (95CI, 0.677–0.914). Use of adjusted ORs, correction for publication bias, sensitivity analysis corroborated these results. ICR and AP were 2.444 and 54.6%. Conclusions: Consistent with stratified analyses reporting non significant/negative associations between alcohol drinking and OC in non multiexposed subjects, an OC preventive activity of drinking is inferable. However, given the high prevalence and the oral carcinogenicity of concomitant drinking and smoking, drinking control policies remain essential.

A comparison of prostate cancer survival in England, Norway and Sweden: A population-based study

2011-08-22

Abstract: Purpose The objective of the study was to compare patterns of survival 2001–2004 in prostate cancer patients from England, Norway and Sweden in relation to age and period of follow-up. Subjects and methods Excess mortality in men with prostate cancer was estimated using nation-wide cancer register data using a period approach for relative survival. 179,112 men in England, 23,192 in Norway and 59,697 in Sweden were included. Results In all age groups, England had the lowest survival, particularly so among men aged 80+. Overall age-standardised five-year survival was 76.4%, 80.3% and 83.0% for England, Norway and Sweden, respectively. The majority of the excess deaths in England were confined to the first year of follow-up. Conclusion The results indicate that a small but important group of older patients present at a late stage and succumb early to their cancers, possibly in combination with severe comorbidity, and this situation is more common in England than in Norway or Sweden.

Survival trends of cancer amongst the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK

2011-09-01

Abstract: Introduction: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults. Methods: Subjects (n=3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan–Meier estimation and Cox regression. Results: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR)=1.75; 95% confidence interval (CI)=1.11–2.76) and lymphoma (HR=2.05; 95% CI=1.09–3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR=0.50; 95% CI=0.28–0.89). This was independent of socioeconomic deprivation. Conclusion: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services.

Expected long-term survival of older patients diagnosed with non-Hodgkin lymphoma in 2008–2012

Dianne Pulte, Adam Gondos, Hermann Brenner — 2011-09-07

Abstract: Background: New therapeutic options have led to substantial increases in survival expectations of patients with non-Hodgkin lymphoma (NHL) in recent years. In contrast to many malignancies, survival in older patients has improved in NHL at a rate similar to that in younger patients. In the past, the impact of innovations on long-term survival of NHL patients on the population level has been disclosed only with substantial delay. Methods: We employ a novel model-based projection method to estimate survival expectations of NHL patients age 60+ diagnosed in 2008–2012. Preliminary empirical evaluation of the method using historical data indicates excellent performance in projection of age specific and overall 5- and 10-year relative survival. Results: Overall 5- and 10-year survival projections for 2008–2012 were 67.5% and 56.9%, respectively, 8.2 percentage units (% units) and 15.2% units, respectively, higher than the most recent survival estimates available from traditional cohort analysis. Projected survival decreased with age, ranging from 79.1% for patients age 60–64 to 54.3% for patients age 80+. Projected survival estimates for diffuse large B-cell lymphoma and follicular lymphoma were 59% and 84.9%, respectively. Survival estimates by model-based projection were substantially higher than available cohort estimates for all age groups including 80+, each specific morphology examined, nodal and extranodal disease, and both genders. Conclusions: Patients over 60 diagnosed with NHL in 2008–2012 have much higher long-term survival expectations than suggested by previously available survival statistics.

Lung cancer and indoor radon exposure in the north of Portugal – An ecological study

Bárbara Veloso, José Rocha Nogueira, Margarida Fonseca Cardoso — 2011-10-26

Abstract: Background: Indoor radon exposure is a well documented environmental factor as a leading cause of lung cancer. Objectives: The aim of this study was to assess the risk of lung cancer and estimate the number of deaths due to indoor radon exposure in the north of Portugal, between 1995 and 2004. Methods: The sixth Biological Effects of Ionizing Radiation Committee (BEIR VI) preferred models were applied to estimate the risk of developing lung cancer induced by indoor radon exposure, by age and level of exposure, and calculated the number of lung cancer deaths attributable to this exposure. Lung cancer mortality data were granted by the North Regional Health Administration and indoor radon concentrations resulted from a national survey conducted by the Portuguese Environmental Agency. The smoking habit was accounted with two methods. A submultiplicative interaction between smoking and indoor radon exposure was considered. Results: Depending on the model applied and the method used to account for the smoking habit, the estimated number of lung cancer deaths attributed to indoor radon exposure, in northern Portugal, ranges from 1565 to 2406, for the period between 1995 and 2004. This indicates that of the 8514 lung cancer deaths observed, from 18 to 28% could be associated with indoor radon exposure.Conclusions: This was the first study realized in Portugal on the impact of indoor radon exposure in lung cancer mortality. The application of the BEIR VI models led to a high number of lung cancer deaths due to indoor radon exposure.

Analysis of microsatellite mutations in buccal cells from a case-control study for lung cancer

2011-07-06

Abstract: Exposure to tobacco carcinogens is the major cause of human lung cancer, but even heavy smokers have only about a 10% life-time risk of developing lung cancer. Currently used screening processes, based largely on age and exposure status, have proven to be of limited clinical utility in predicting cancer risk. More precise methods of assessing an individual's risk of developing lung cancer are needed. Because of their sensitivity to DNA damage, microsatellites are potentially useful for the assessment of somatic mutational load in normal cells. We assessed mutational load using hypermutable microsatellites in buccal cells obtained from lung carcinoma cases and controls to test if such a measure could be used to estimate lung cancer risk. There was no significant association between smoking status and mutation frequency with any of the markers tested. No significant association between case status and mutation frequency was observed. Age was significantly related to mutation frequency in the microsatellite marker D7S1482. These observations indicate that somatic mutational load, as measured using mutation frequency of microsatellites in buccal cells, increases with increasing age but that subjects who develop lung cancer have a similar mutational load as those who remain cancer free. This finding suggests that mutation frequency of microsatellite mutations in buccal cells may not be a promising biomarker for lung cancer risk.

Activation of apoptosis by ethyl acetate fraction of ethanol extract of Dianthus superbus in HepG2 cell line

2011-09-19

Abstract: Dianthus superbus L. is commonly used as a traditional Chinese medicine. We recently showed that ethyl acetate fraction (EE-DS) from ethanol extract of D. superbus exhibited the strongest antioxidant and cytotoxic activities. In this study, we examined apoptosis of HepG2 cells induced by EE-DS, and the mechanism underlying apoptosis was also investigated. Treatment of HepG2 cells with EE-DS (20–80μg/ml) for 48h led to a significant dose-dependent increase in the percentage of cells in sub-G1 phase by analysis of the content of DNA in cells, and a large number of apoptotic bodies containing nuclear fragments were observed in cells treated with 80μg/ml of EE-DS for 24h by using Hoechst 33258 staining. These data show that EE-DS can induce apoptosis of HepG2 cells. Immunoblot analysis showed that EE-DS significantly suppressed the expressions of Bcl-2 and NF-κB. Treatment of cells with EE-DS (80μg/ml) for 48h resulted in significant increase of cytochrome c in the cytosol, which indicated cytochrome c release from mitochondria. Activation of caspase-9 and -3 were also determined when the cells treated with EE-DS. The results suggest that apoptosis of HepG2 cells induced by EE-DS could be through the mitochondrial intrinsic pathway. High performance liquid chromatography (HPLC) data showed that the composition of EE-DS is complicated. Further studies are needed to find the effective constituents of EE-DS.

Determination of whole body circadian phase in lung cancer patients: Melatonin vs. cortisol

Gianluigi Mazzoccoli, Francesco Giuliani, Robert B. Sothern — 2011-07-15

Abstract: Background: A quantifiable and reliable technique for the determination of body circadian phase applicable to non-laboratory studies would allow the evaluation of circadian dysregulation. In this study we evaluated feasible methodologies to individualize whole body circadian phase in lung cancer patients. Methods: Cortisol and melatonin serum levels were measured in blood samples collected every 4h for 24h from eleven male controls and nine men suffering from non-small cell lung cancer. Circadian rhythmicity was evaluated and the 4-hourly fractional variations (FV) were calculated to evaluate the dynamics of the rise and fall in serum levels. Results: Overall cortisol serum levels were higher in cancer patients (p<0.001), and lower for melatonin, but not significantly (p=0.261). Original serum levels of cortisol and melatonin each showed a prominent 24h oscillation in both study groups, with highest values at night for melatonin and near awakening for cortisol. Using all data after normalization to percent of individual mean, ANOVA detected a significant time-effect (p<0.001) and cosinor analysis detected a significant 24h rhythm (p<0.001) in each group. Overall fractional variation (FV) levels were lower for cortisol in cancer patients and higher for melatonin, but these differences were not significant. FV levels of cortisol and melatonin each showed a prominent 24h oscillation in both study groups, with highest values prior to darkness onset for melatonin and near mid-dark for cortisol. ANOVA also detected a significant time-effect (p<0.002) and cosinor analysis detected a significant 24h rhythm (p<0.001) for FV in each group, with maximal FV preceding maximal serum levels by ∼3h for melatonin and ∼5h for cortisol. Conclusions: A chronobiological evaluation of serum levels and fractional variations for cortisol and especially melatonin is a valuable methodology to define body circadian phase in lung cancer patients. It is possible to describe the complex process of hormone secretion with a methodology that allows the definition of both temporal characteristics and dynamic components. Impact: This kind of analysis might be useful in the study of hormone secretion(s) in cancer patients and other diseases and to guide therapeutic interventions. While lung cancer patients may have a negative prognostic value based upon stage and/or other hormonal aspects of their hypothalamus–pituitary–thyroid–adrenal axis function, patients that nevertheless maintain circadian rhythmicity in key body rhythm markers may still be eligible candidates for a chronotherapeutic approach of treatment(s).

Evaluating the long-term effect of FOBT in colorectal cancer screening

Dianhong Luo, Alexander C. Cambon, Dongfeng Wu — 2011-10-31

Abstract: Background: Cancer screening has been effective in detecting tumors early before symptoms appear. However, the effectiveness of the regular fecal occult blood test (FOBT) in colorectal cancer in the long term has not been quantified.Methods: We applied the statistical method developed by Wu and Rosner using data from the Minnesota Colon Cancer Control Study (MCCCS). All initially asymptomatic participants were classified into four mutually exclusive groups: true-early-detection, no-early-detection, over-diagnosis, and symptom-free life; human lifetime was treated as a random variable and is subject to competing risks. All participants in the screening program will eventually fall into one of the four outcomes above. Predictive inferences on the percentages of the four outcomes for both genders were made using the Minnesota study data.Results: Depending on gender, screening frequency and age at the initial screening, for all participants the probability of “symptom-free-life” varies between 95.3% and 96.6%; the probability of “true-early-detection” is 1.9–3.8%; the probability of no-early-detection is 0.3–2.0%; the probability of over-diagnosis is 0.16–0.3%. Among those with colorectal cancer detected by regular FOBT, the probability of over-diagnosis is lower than expected and is between 6% and 9%, with 95% CI (2.5%, 21.3%) for females and (1.9%, 44.7%) for males. The probability of true-early-detection increases as screening interval decreases. The probability of no-early-detection decreases as screening interval decreases.Conclusion: The probability of over-diagnosis among the screen-detected cases is not as high as previously thought. We hope this outcome can provide valuable information on the effectiveness of the FOBT in colorectal cancer detection in the long term.

Serum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasis

Long-gang Wang, Jin Gu — 2011-05-25

Abstract: Background: Colorectal cancer (CRC) metastasis occurs in various organs, most frequently in liver. Serological examination including tumor and biochemical markers for liver function evaluation is routinely performed, though its accuracy is not high. MicroRNAs (miRNAs) have been implicated in a variety of human diseases including cancer, and have many characteristics of an ideal biomarker most notably their inherent stability and resilience. Recently, several studies have indicated that circulating miRNAs hold much potential as novel noninvasive biomarkers for cancer and other disease processes. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for CRC with liver metastasis. Methods: This study was divided into three phases: (I) 3 candidate serum miRNAs were detected by using real-time RT-PCR, corresponding 38 CRC patients with liver metastasis and 36 CRC patients without metastasis. (II) Marker validation by real-time RT-PCR on a similar cohort of age- and sex-matched CRC patients without (n=20) and with liver metastasis (n=20). (III) We examined the correlation between the expressions of candidate serum miRNAs with clinical parameters of CRC patients. Results: Serum miR-29a was significantly higher in colorectal liver metastasis (CRLM) patients than in CRC patients. This marker yielded a receiver operating characteristic curve area of 80.3%. At a cutoff value of 0.155, the sensitivity was 75% and the specificity was 75% in discriminating metastatic from non-metastatic patients. In addition, increased levels of miR-29a expression were also observed in colorectal tumors from CRLM patients compared with CRC patients. No significant difference was observed in the levels of serum miR-92a between metastatic and non-metastatic patients. Conclusions: These findings suggest that serum miR-29a has strong potential as a novel noninvasive biomarker for early detection of CRC with liver metastasis.

Cancer Epidemiology

Editorial Board

Table of Contents

Africa's growing cancer burden: Environmental and occupational contributions

Time trends and age–period–cohort analyses on incidence rates of nasopharyngeal carcinoma during 1993–2007 in Wuhan, China

Time trends in testicular cancer in Croatia 1983–2007: Rapid increases in incidence, no declines in mortality

Comparison of methods for calculating relative survival in population-based studies

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States

Using method triangulation to validate a new instrument (CPWQ-com) assessing cancer patients’ satisfaction with communication

Comparison of racial differences in childhood cancer risk in case-control studies and population-based cancer registries

Family history of cancer and non-malignant diseases and risk of childhood acute lymphoblastic leukemia: A Children's Oncology Group Study

Anthropometric factors, physical activity, and risk of Non-Hodgkin's lymphoma in the Women's Health Initiative

Main dietary compounds and pancreatic cancer risk. The quantitative analysis of case–control and cohort studies

CYP1AI, glutathione S-transferase gene polymorphisms and risk of Polycythemia vera

Detection of methylated tissue factor pathway inhibitor 2 and human long DNA in fecal samples of patients with colorectal cancer in China

Meta-analysis of cancer risk in folic acid supplementation trials

Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system

Breast-conserving therapy versus modified radical mastectomy: Socioeconomic status determines who receives what—Results from case–control study in Tianjin, China

Biochemical-markers for the diagnosis of bone metastasis: A clinical review

Revisiting the association between alcohol drinking and oral cancer in nonsmoking and betel quid non-chewing individuals

A comparison of prostate cancer survival in England, Norway and Sweden: A population-based study

Survival trends of cancer amongst the south Asian and non-south Asian population under 30 years of age in Yorkshire, UK

Expected long-term survival of older patients diagnosed with non-Hodgkin lymphoma in 2008–2012

Lung cancer and indoor radon exposure in the north of Portugal – An ecological study

Analysis of microsatellite mutations in buccal cells from a case-control study for lung cancer

Activation of apoptosis by ethyl acetate fraction of ethanol extract of Dianthus superbus in HepG2 cell line

Determination of whole body circadian phase in lung cancer patients: Melatonin vs. cortisol

Evaluating the long-term effect of FOBT in colorectal cancer screening

Serum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasis