Bas A.J. Verhage

A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk

Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow‐up. Study‐specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21–22.9 kg/m2, pancreatic cancer risk was 47% higher (95%CI:23–75%) among obese (BMI ≥ 30 kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09–1.56 comparing BMI ≥ 25 kg/m2 to a BMI between 21 and 22.9 kg/m2). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m2) and not obese at baseline (BMI < 30 kg/m2), pancreatic cancer risk was 54% higher (95%CI = 24–93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≥ 10 kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03–1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.

ALCOHOL INTAKE AND PANCREATIC CANCER RISK: A POOLED ANALYSIS OF FOURTEEN COHORT STUDIES

Background: Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk. Methods: We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks and 95% confidence intervals were calculated using Cox proportional hazards models and then pooled using a random effects model. Results: A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate relative risk, 1.22; 95% confidence interval, 1.03-1.45 comparing ≥30 to 0 grams/day of alcohol; P value, test for between-studies heterogeneity = 0.80). For this comparison, the positive association was only statistically significant among women although the difference in the results by gender was not statistically significant (P value, test for interaction = 0.19). Slightly stronger results for alcohol intake were observed when we limited the analysis to cases with adenocarcinomas of the pancreas. No statistically significant associations were observed for alcohol from wine, beer, and spirits comparing intakes of ≥5 to 0 grams/day. A stronger positive association between alcohol consumption and pancreatic cancer risk was observed among normal weight individuals compared with overweight and obese individuals (P value, test for interaction = 0.01). Discussion: Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day. (Cancer Epidemiol Biomarkers Prev 2009;18(3):765–76)

Fruit and vegetable consumption and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Many case‐control studies have suggested that higher consumption of fruit and vegetables is associated with a lower risk of pancreatic cancer, whereas cohort studies do not support such an association. We examined the associations of the consumption of fruits and vegetables and their main subgroups with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is comprised of over 520,000 subjects recruited from 10 European countries. The present study included 555 exocrine pancreatic cancer cases after an average follow‐up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models, stratified by age at recruitment, gender, and study center, and adjusted for total energy intake, weight, height, history of diabetes mellitus, and smoking status. Total consumption of fruit and vegetables, combined or separately, as well as subgroups of vegetables and fruits were unrelated to risk of pancreatic cancer. Hazard ratios (95% CI) for the highest versus the lowest quartile were 0.92 (0.68–1.25) for total fruit and vegetables combined, 0.99 (0.73–1.33) for total vegetables, and 1.02 (0.77–1.36) for total fruits. Stratification by gender or smoking status, restriction to microscopically verified cases, and exclusion of the first 2 years of follow‐up did not materially change the results. These results from a large European prospective cohort suggest that higher consumption of fruit and vegetables is not associated with decreased risk of pancreatic cancer.

Single‐nucleotide polymorphism in the E‐cadherin gene promoter modifies the risk of prostate cancer

E‐cadherin plays a major role in intercellular adhesion, cell polarity and tissue architecture. We determined the relative risk of PCa associated with a previously reported C/A SNP at −160 bp relative to the transcription‐start site of the E‐cadherin gene promoter. Eighty‐two PCa patients and 188 controls were genotyped. Genotype and allele frequencies differed significantly among cases and controls. A‐allele carriers had a higher relative risk of PCa (OR = 3.6, 95% CI 2.0–6.4) compared to C‐only carriers. AC and AA genotypes had an increased risk of PCa (OR = 3.8, 95% CI 2.1–6.8 and OR = 1.7, 95% CI 0.4–6.6, respectively) compared to CC genotypes.

Meat and fat intake and pancreatic cancer risk in the Netherlands Cohort Study

Meat contains numerous carcinogens, such as heterocyclic amines, polycyclic aromatic hydrocarbons, and N‐nitroso compounds, which can be derived either from natural food or during the process of food preparation. These carcinogens may increase pancreatic cancer risk. Furthermore, studies in animals showed that polyunsaturated fatty acids, especially linoleic acid, increase pancreatic cancer risk. We examined prospectively the relation between pancreatic cancer risk and intake of fresh meat, processed meat, fish, eggs, total fat, and different types of fat. The Netherlands Cohort Study consisted of 120,852 men and women who completed a baseline questionnaire in 1986. After 13.3 years of follow‐up, 350 pancreatic cancer cases (66% microscopically confirmed) were available for analysis. A validated 150‐item food‐frequency questionnaire was used to calculate intake of fresh meat, processed meat, fish, eggs, fat and different types of fat. No association was found when examining the association between intake of fresh meat, other types of meat, fish, eggs, dietary intake of total fat and different types of fat and risk of pancreatic cancer. It is important for future studies to investigate the relation between different meat‐cooking methods and pancreatic cancer.

Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis

In a cohort study, ovarian cancer (280 cases) showed no significant association with tea or coffee, the multivariable rate ratios being 0.94 (95% confidence interval (CI): 0.89, 1.00) and 1.04 (95% CI: 0.97, 1.12) per cup per day, respectively. A meta-analysis also produced no significant findings overall, though the cohort studies showed a significant inverse association for tea.

Intake of vegetables, fruits, carotenoids and vitamins C and E and pancreatic cancer risk in The Netherlands Cohort Study

Epidemiological data investigating the relation between fruit and vegetable consumption and pancreatic cancer risk have shown inconsistent results so far. Most case‐control studies observed an inverse association with total fruit and vegetable consumption, whereas results from most cohort studies have largely been null. We examined prospectively the relation between pancreatic cancer risk and intake of vegetables, fruits, carotenoids and vitamins C and E. The Netherlands Cohort Study consisted of 120,852 men and women who completed a questionnaire at baseline in 1986, including a validated 150‐item food‐frequency questionnaire. After 16.3 years of follow‐up, 423 cases were available for analysis. Total vegetable and total fruit consumption were not associated with pancreatic cancer risk (highest vs. lowest quintile, multivariable‐adjusted hazard rate ratio = 1.23, 95% confidence interval: 0.86‐1.75 and multivariable‐adjusted hazard rate ratio = 0.90, 95% confidence interval: 0.66‐1.24, respectively). Also, for cooked vegetables, raw vegetables and vegetables and fruits classified into subgroups, no associations were observed. Dietary carotenoids, vitamin C and E intake and supplements containing vitamin C or E were not associated with pancreatic cancer risk. The results were not modified by sex, smoking status and body mass index. In conclusion, we observed no association between a high consumption of vegetables and fruits and pancreatic cancer risk in this large cohort study, which is in agreement with previous prospective studies. Furthermore, we observed no association between the intake of carotenoids, vitamins and vitamin supplements and pancreatic cancer risk.

Dietary Flavonoid Intake, Black Tea Consumption, and Risk of Overall and Advanced Stage Prostate Cancer

Flavonoids are natural antioxidants found in various foods, and a major source is black tea. Some experimental evidence indicates that flavonoids could prevent prostate cancer. We investigated the associations between flavonoid intake, black tea consumption, and prostate cancer risk in the Netherlands Cohort study, which includes 58,279 men who provided detailed baseline information on several cancer risk factors. From 1986 to 2003, 3,362 prostate cancers were identified, including 1,164 advanced (stage III/IV) cancers. Cox proportional hazards regression using the case-cohort approach was used to estimate hazard ratios and 95% confidence intervals. Intake of total catechin, epicatechin, kaempferol, and myricetin and consumption of black tea were associated with a decreased risk of stage III/IV or stage IV prostate cancer. Hazard ratios of stage III/IV and stage IV prostate cancer for the highest versus the lowest category of black tea consumption (≥5 versus ≤1 cups/day) were 0.75 (95% confidence interval: 0.59, 0.97) and 0.67 (95% confidence interval: 0.50, 0.91), respectively. No associations were observed for overall and nonadvanced prostate cancer. In conclusion, dietary flavonoid intake and black tea consumption were associated with a decreased risk of advanced stage prostate cancer.

Advanced prostate cancer risk in relation to toenail selenium levels.

BACKGROUND Selenium may prevent advanced prostate cancer (PCa), but most studies on this topic were conducted in populations with moderate to high selenium status. We investigated the association of toenail selenium, reflecting long-term selenium exposure, and advanced PCa risk in a population from the Netherlands where low selenium status is widespread. METHODS The analysis was conducted in the prospective Netherlands Cohort Study, which included 58 279 men aged 55 to 69 years at baseline in 1986. All cohort members completed a baseline questionnaire, and approximately 79% of participants provided toenail clippings, which were used for toenail selenium measurements using instrumental neutron activation analysis. Incident advanced PCa case subjects from the entire cohort were identified during 17.3 years of follow-up. The study employed a case-cohort design for which a random subcohort was sampled at baseline. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. All tests were two-sided. RESULTS Complete toenail selenium data were available for 898 advanced (International Union Against Cancer stage III/IV) PCa case subjects and 1176 subcohort members. The average toenail selenium concentration of subcohort members was 0.550 µg/g. Toenail selenium was associated with a reduced risk of advanced PCa; adjusted hazard ratio for the highest vs lowest quintile was 0.37 (95% CI = 0.27 to 0.51; P trend < .001). For stage IV PCa, men in the highest vs lowest quintile of toenail selenium had an adjusted hazard ratio of 0.30 (95% CI = 0.21 to 0.45; P trend < .001). CONCLUSIONS Toenail selenium was associated with a substantial decrease in risk of advanced PCa.

Dietary Folate and Folate Vitamers and the Risk of Pancreatic Cancer in the Netherlands Cohort Study

An association between high intake of folate and reduced risk of cancer has been suggested by previous research. However, epidemiologic data from cohort studies regarding the relationship between dietary folate and pancreatic cancer are sparse and inconsistent. We examined the association between dietary folate intake and risk of pancreatic cancer within the Netherlands Cohort Study on diet and cancer. Men and women (120,852), ages 55 to 69 years, were recruited. Information on diet was collected at baseline by means of food frequency questionnaires, and the cohort was followed for 13.3 years. Total folate and vitamer intake were calculated using folate contents of food items derived from a validated liquid chromatography trienzyme method. Cases (n = 363) were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. A case-cohort approach was used using the follow-up data of a random subcohort (n = 5,000) identified at the onset of the cohort. Multivariable hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards model. After adjusting for age, gender, smoking status, number of years smoked, number of cigarettes smoked per day, and intake of added sugar multivariate hazard ratio comparing the highest and lowest quintiles of folate intake for pancreatic cancer risk was 1.37 (confidence interval, 0.97-1.94; Ptrend = 0.07). When folate vitamers were analyzed separately, results did not show a difference in association. Our results do not support a protective association of total dietary folate or individual folate vitamers on the risk of pancreatic cancer.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1785–91)