Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data.

Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene-smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level.

Prostate cancer (PCa) risk variants and risk of fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

Background: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM).

Objective: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.

Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk.

Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer.

Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk.

Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort.

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported.

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: evidence from the EPIC cohort.

To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years.

Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study.

Background: The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain.

Methods: Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors.

Results: A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs.

Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk-results from the EPIC cohort study.

Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.

Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer.

Background: Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations.

Methods: The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition.

Dietary intakes and risk of lymphoid and myeloid leukemia in the European Prospective Investigation into Cancer and Nutrition (EPIC).

The etiology of leukemias cannot entirely be explained by known risk factors, including ionizing radiation, benzene exposure, and infection with human T cell leukemia virus. A number of studies suggested that diet influences the risk of adult leukemias. However, results have been largely inconsistent.

Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort.

Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study.

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study.

Background: A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change.

Objective: We investigated the relation between BMI and weight change and subsequent colon and rectal cancer risk.

Adherence to the Dutch Guidelines for a Healthy Diet and cancer risk in the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort.

Objective: To examine the association between adherence to the Dutch Guidelines for a Healthy Diet created by the Dutch Health Council in 2006 and overall and smoking-related cancer incidence.

Design: Prospective cohort study.

Setting: Adherence to the guidelines, which includes one recommendation on physical activity and nine on diet, was measured using an adapted version of the Dutch Healthy Diet (DHD) index.

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort.

Purpose: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations.

Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis.

Background: Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level.

Methods: Using genome-wide association studies (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by using the likelihood-ratio test nested in logistic regression models and Ingenuity Pathway Analysis (IPA).

Circulating soluble CD27 and CD30 in workers exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD).

Previous studies suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings remain inconclusive. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. In this cross-sectional study, we investigated changes in plasma levels of interleukin 1 receptor antagonist (IL1RA) and soluble (s)CD27 and sCD30 which have been found to be predictive of lymphoma, among workers of a cohort occupationally exposed to TCDD.

Development of methodology for disability-adjusted life years (DALYs) calculation based on real-life data.

Background: Disability-Adjusted Life Years (DALYs) have the advantage that effects on total health instead of on a specific disease incidence or mortality can be estimated. Our aim was to address several methodological points related to the computation of DALYs at an individual level in a follow-up study.

Methods: DALYs were computed for 33,507 men and women aged 20-70 years when participating in the EPIC-NL study in 1993-7.

An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.

Purpose: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer.

Patients And Methods: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates.

Role of dietary factors in survival and mortality in colorectal cancer: a systematic review.

The role of dietary factors in the outcome of colorectal cancer (CRC) has been the subject of many studies, but results are inconclusive. Presented here are the results of a systematic review of studies published on dietary factors and CRC outcome in the English literature between March 2002 and March 2012. Studies were subdivided into survival studies in CRC patients and CRC mortality studies in the general population.

The contribution of diet and lifestyle to socioeconomic inequalities in cardiovascular morbidity and mortality.

Background: The role of differences in diet on the relationship between socioeconomic factors and cardiovascular diseases remains unclear. We studied the contribution of diet and other lifestyle factors to the explanation of socioeconomic inequalities in cardiovascular diseases.

Methods: We prospectively examined the incidence of coronary heart disease (CHD) and stroke events amongst 33,106 adults of the EPIC-NL cohort.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

Background: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent.

Methods: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models.

Results: The OR for pancreatic cancer was 1.

Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline.

Adherence to the WHO's healthy diet indicator and overall cancer risk in the EPIC-NL cohort.

Background: A healthy dietary pattern defined by international recommendations of the World Health Organisation (WHO) has been shown to reduce overall mortality risk. It is unknown whether this healthy dietary pattern is associated with overall cancer incidence.

Design: In total 35,355 men and women within the Dutch European Prospective Investigation into Cancer and Nutrition-cohort were followed for cancer occurrence.

Serum metabolomic pertubations among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with multiple health effects. Mechanistic studies using metabolomics could provide supporting evidence for such associations by identifying relevant biological pathways. In this study, we investigated metabolic perturbations in a cohort of TCDD exposed workers to better understand TCDD related health effects.

Lifestyle, dietary factors, and antibody levels to oral bacteria in cancer-free participants of a European cohort study.

Background: Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked to several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria.