Françoise Clavel-Chapelon

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 520u2009000 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.

Menopausal Hormone Therapy and Risk of Endometrial Carcinoma Among Postmenopausal Women in the European Prospective Investigation into Cancer and Nutrition

Estrogen-only menopausal hormone therapy (HT) increases the risk of endometrial cancer, but less is known about the association with other types of HT. Using Cox proportional hazards regression, the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospective Investigation into Cancer and Nutrition between 1992 and 2000. After a mean follow-up period of 9 years, 601 incident cases of endometrial cancer were identified. In comparison with never users of HT, risk of endometrial cancer was increased among current users of estrogen-only HT (hazard ratio (HR) = 2.52, 95% confidence interval (CI): 1.77, 3.57), tibolone (HR = 2.96, 95% CI: 1.67, 5.26), and, to a lesser extent, estrogen-plus-progestin HT (HR = 1.41, 95% CI: 1.08, 1.83), although risks differed according to regimen and type of progestin constituent. The association of HT use with risk was stronger among women who were older, leaner, or had ever smoked cigarettes. The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk. The increased risk associated with tibolone use requires further investigation.

Hormonal, Metabolic, and Inflammatory Profiles and Endometrial Cancer Risk Within the EPIC Cohort—A Factor Analysis

A Western lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled insulin resistance/metabolic syndrome, steroids, and inflammation factors. A fourth component, lipids, was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.

Dietary fiber intake and risk of hormonal receptor–defined breast cancer in the European Prospective Investigation into Cancer and Nutrition study

BACKGROUNDnLimited scientific evidence has characterized the association between dietary fiber intake and risk of breast cancer (BC) by menopausal status and hormone receptor expression in tumors.nnnOBJECTIVEnWe investigated the relation between total dietary fiber and its main food sources (vegetables, fruit, cereals, and legumes) and BC risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC).nnnDESIGNnA total of 11,576 invasive BC cases in 334,849 EPIC women mostly aged 35-70 y at baseline were identified over a median follow-up of 11.5 y. Dietary fiber was estimated from country-specific dietary questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk with energy adjustment by using the residual method. Subgroup analyses were performed by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) expression in tumors.nnnRESULTSnBC risk was inversely associated with intakes of total dietary fiber [hazard ratio comparing fifth quintile to first quintile (HR(Q5-Q1)): 0.95; 95% CI: 0.89, 1.01; P-trend = 0.03] and fiber from vegetables (0.90; 0.84, 0.96; P-trend < 0.01) but not with fiber from fruit, cereals, or legumes. Overall, associations were homogeneous by menopausal status and ER and PR expression in tumors. For vegetable fiber, stronger associations were observed for estrogen receptor-negative and progesterone receptor-negative (HR(Q5-Q1):0.74; 95% CI: 0.59, 0.93; P-trend = 0.01) than for estrogen receptor-positive and progesterone receptor-positive tumors (0.92: 0.81, 1.03; P-trend = 0.05), with P-heterogeneity = 0.09.nnnCONCLUSIONnDiets rich in dietary fiber and, particularly, fiber from vegetables may be associated with a small reduction in risk of BC, independently of menopausal status.

Flavonoid intake and incident hypertension in women

BACKGROUNDnIntake of flavonoid-containing food has been shown to have a beneficial effect on blood pressure in short-term randomized trials. There are limited data on total flavonoid and flavonoid-subclass consumption over a long period of time and the corresponding incidence of hypertension.nnnOBJECTIVEnWe aimed to evaluate the relation between flavonoid subclasses and total flavonoid intakes and incidence of hypertension.nnnDESIGNnIn a prospective cohort of 40,574 disease-free French women who responded to a validated dietary questionnaire, we observed 9350 incident cases of hypertension between 1993 and 2008. Cases were identified through self-reports of diagnosed or treated hypertension. Multivariate Cox regression models were adjusted for age, family history of hypertension, body mass index, physical activity, smoking, diabetes, hypercholesterolemia, hormone therapy, and alcohol, caffeine, magnesium, potassium, omega-3 (n-3), and processed meat intakes.nnnRESULTSnWomen in the highest quintile of flavonol intake had a 10% lower rate of hypertension than women in the lowest quintile (HR: 0.90; 95% CI: 0.84, 0.97;P-trend = 0.031). Similarly, there was a 9% lower rate for women in the highest category of intake than for women in the lowest category of intake for both anthocyanins and proanthocyanidin polymers [HRs: 0.91 (95% CI: 0.84, 0.97;P-trend = 0.0075) and 0.91 (95% CI: 0.85, 0.97;P-trend = 0.0051), respectively]. An inverse association for total flavonoid intake was observed with a similar magnitude.nnnCONCLUSIONnIn this large prospective cohort of French middle-aged women, participants with greater flavonol, anthocyanin, and polymeric flavonoid intakes and greater total flavonoid intake were less likely to develop hypertension.

Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

BACKGROUNDnThe consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well.nnnOBJECTIVEnWe examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk.nnnDESIGNnThe study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa.nnnRESULTSnTotal soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake.nnnCONCLUSIONSnSoft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and nectar subtypes are warranted to clarify these results.

Serum Sex Steroids in Premenopausal Women and Breast Cancer Risk Within the European Prospective Investigation Into Cancer and Nutrition (EPIC)

BACKGROUNDnContrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian androgen excess and progesterone deficiency, estrogen excess, estrogen and progesterone excess, and both an excess or lack of adrenal androgens (dehydroepiandrosterone [DHEA] or its sulfate [DHEAS]) as risk factors. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk.nnnMETHODSnLevels of DHEAS, (Delta4-)androstenedione, testosterone, and sex hormone binding globulin (SHBG) were measured in single prediagnostic serum samples from 370 premenopausal women who subsequently developed breast cancer (case patients) and from 726 matched cancer-free control subjects. Levels of progesterone, estrone, and estradiol were also measured for the 285 case patients and 555 matched control subjects who had provided information about the day of menstrual cycle at blood donation. Conditional logistic regression models were used to estimate relative risks of breast cancer by quartiles of hormone concentrations. All statistical tests were two-sided.nnnRESULTSnIncreased risks of breast cancer were associated with elevated serum concentrations of testosterone (odds ratio [OR] for highest versus lowest quartile = 1.73, 95% confidence interval [CI] = 1.16 to 2.57; P(trend) = .01), androstenedione (OR for highest versus lowest quartile = 1.56, 95% CI = 1.05 to 2.32; P(trend) = .01), and DHEAS (OR for highest versus lowest quartile = 1.48, 95% CI = 1.02 to 2.14; P(trend) = .10) but not SHBG. Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk (OR for highest versus lowest quartile = 0.61, 95% CI = 0.38 to 0.98; P(trend) = .06). The absolute risk of breast cancer for women younger than 40 followed up for 10 years was estimated at 2.6% for those in the highest quartile of serum testosterone versus 1.5% for those in the lowest quartile; for the highest and lowest quartiles of progesterone, these estimates were 1.7% and 2.6%, respectively. Breast cancer risk was not statistically significantly associated with serum levels of the other hormones.nnnCONCLUSIONSnOur results support the hypothesis that elevated blood concentrations of androgens are associated with an increased risk of breast cancer in premenopausal women.