Carla H. van Gils

Association between Pre-Diagnostic Circulating Vitamin D Concentration and Risk of Colorectal Cancer in European Populations: a Nested Case-Control Study

Objective To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. Design Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. Participants 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls Main outcome measures Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. Results 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); ≥100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

Fruit and vegetable consumption and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

IntroductionLymphomas are a heterogeneous group of malignant diseases of cells of the immune system. The best-established risk factors are related to dys-regulation of immune function, and evidence suggests that factors such as dietary or lifestyle habits may be involved in the etiology.Material and methodsIn the European Prospective Investigation into Cancer and Nutrition (EPIC), 849 lymphoma cases were identified in a median follow-up period of 6.4 years. Fruit and vegetable consumption was estimated from validated dietary questionnaires. Cox proportional hazard models were used to examine the association between fruit and vegetable intake with the risk of lymphomas overall and subentities.ResultsThere was no overall association between total fruit and vegetable consumption and risk of lymphoma [hazard ratio (HR) = 0.95, 95% confidence interval (CI) 0.78–1.15 comparing highest with lowest quartile]. However, the risk of diffuse large B-cell lymphomas (DLBCL) tended to be lower in participants with a high intake of total vegetables (HR = 0.49, 95% CI 0.23–1.02).ConclusionIn this large prospective study, an inverse associations between fruit and vegetable consumption and risk of lymphomas overall could not be confirmed. Associations with lymphoma subentities such as DLBCL warrant further investigation.

Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort.

Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index. Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001). Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels. Impact: This study strengthens the evidence for the benefits of a smoking ban in public places. Cancer Epidemiol Biomarkers Prev; 20(5); 869–75. ©2011 AACR.

Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women

ObjectiveLifetime cumulative number of menstrual cycles is related to breast cancer risk. The aim of this study is to investigate the relation between this index and serum sex hormone levels in postmenopausal women.MethodsCross-sectional study including 860 naturally postmenopausal Dutch participants of the European Prospective Investigation into Cancer and Nutrition. Lifetime cumulative number of menstrual cycles was computed using questionnaire data on ages at menarche and menopause, number of pregnancies, breastfeeding, oral contraceptive use (OC) and regularity pattern. Measurements of hormones included estrone (E1), estradiol (E2), andostrenedione, testosterone, sex-hormone binding globulin (SHBG) and dehydroepiandrostenedione sulfate (DHEAS). The relation between the lifetime cumulative number of menstrual cycles and hormone levels was assessed using analysis of covariance. Relations between reproductive characteristics and hormone levels were also studied. Adjustments for characteristics at blood collection included age, years since menopause, BMI, hormone replacement therapy use, OC use, smoking habits, alcohol intake and physical activity were done.ResultsLifetime cumulative number of cycles was related with SHBG; participants in the lowest category had higher SHBG levels. For the separate characteristics, DHEAS and androstenedione increased significantly with increasing age at menarche, while androstenedione and testosterone decreased with increasing age at menopause. For the parity characteristics, SHBG levels increased according to the number of live births.ConclusionsLifetime cumulative number menstrual cycles was related only to SHBG. Therefore, free levels of estrogens or androgens may be related to this number of menstrual cycles estimate, reflecting lifetime exposure to ovarian hormones.

Alcohol intake and breast cancer in the European Prospective investigation into Cancer and Nutrition : Short title

Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35–70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country‐specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person‐years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7–5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1–11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER−/PR−, HER2− and ER−/PR−HER2− tumors. Breast cancer risk was stronger among women who started drinking prior to first full‐time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption.

Abstract B77: Short-term weight change and colon and rectal cancer risk in the EPIC cohort

Background: BMI (Body Mass Index) has been considered as a risk factor for colon cancer but not for rectal cancer. Less is known about the association between weight change and colon and rectal cancer risk. In this study we investigated how risk for colon and rectal cancer develops for weight change within the follow-up period of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. Methods: We investigated the relationship between weight change and subsequent colon and rectal cancer risk among 328.781 participants aged between 25 and 70 years from the EPIC cohort. EPIC is a large ongoing European study in 23 centres in 10 European countries. At recruitment (1992-2000), weight, height and waist circumference were measured and detailed dietary and lifestyle data were collected through questionnaires. Body weight was reassessed on average 5 years after recruitment (range 0.3 - 13 years) and was mainly self-reported. In the subsequent years, participants were followed for the occurrence of cancer for up to 13 years. We used Cox regression analysis, with age as the time variable, and stratified the models according to study center and age, with further adjustment for body mass index (BMI) and waist circumference at recruitment, smoking status and intensity, physical activity, educational level, alcohol intake and intake of fibres, vegetables, fruits, fish and meat. In women we additionally adjusted for menopausal status, use of oral contraceptives and use of hormone replacement therapy. Weight change (kg/year) was defined as sex specific quintiles, with the combined quintiles 2 and 3 as the reference category defined as those with stable weight (i.e. weight change of -2.9 to 1.4 kg per 5 years in men; and -1.9 to 1.9 kg per 5 years in women). Results: During 2.1 million person-years (mean duration of follow-up 6.4 years) after the second assessment of weight, 480 and 781 incident colon cancer and 354 and 393 rectal cancer cases were identified in men and women, respectively. Moderate weight gain was associated with an increased risk of colon cancer in men (weight gain of 1.4 -3.8kg/ 5 years; 4th quintile, HR 1.32; 95% CI 1.03; 1.69) and women (weight gain of 1.9-4.2 kg/ 5 years; 4th quintile, HR 1.29; 95% CI 0.99; 1.68). No effects were found for higher weight gain, or for the relationship between weight gain and rectal cancer risk in both men and women. There was no interaction between weight change and BMI, waist circumference or hormone replacement therapy. Conclusion: Our preliminary results indicate that the risk on colon cancer is increased in men and women with moderate short term weight gain, but not in those with high weight gain. The latter might be due to competing risks in men with high weight gain. This finding needs further investigation and will be discussed at the conference in more detail. Citation Format: Charlotte Noelle Steins Bisschop, Carla H. van Gils, Marleen J. Emaus, Bas Bueno de Mesquita, Krasimira Aleksandrova, Heiner Boeing, Mazda Jenab, Elio Riboli, Teresa Norat, Petra H.M. Peeters, Anne M. May. Short-term weight change and colon and rectal cancer risk in the EPIC cohort. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B77.