Dietary, lifestyle and clinicopathological factors associated with APC mutations and promoter methylation in colorectal cancers from the EPIC-Norfolk study.

The tumour suppressor APC is the most commonly altered gene in colorectal cancer (CRC). Genetic and epigenetic alterations of APC may therefore be associated with dietary and lifestyle risk factors for CRC. Analysis of APC mutations in the extended mutation cluster region (codons 1276-1556) and APC promoter 1A methylation was performed on 185 archival CRC samples collected from participants of the European Prospective Investigation into Cancer (EPIC)-Norfolk study, with the aim of relating these to high-quality seven-day dietary and lifestyle data collected prospectively.

MLH1 promoter methylation, diet, and lifestyle factors in mismatch repair deficient colorectal cancer patients from EPIC-Norfolk.

There is conflicting evidence for the role diet and lifestyle play in the development of mismatch repair (MMR)-deficient colorectal cancers (CRC). In this study, associations between MMR deficiency, clinicopathological characteristics, and dietary and lifestyle factors in sporadic CRC were investigated. Tumor samples from 185 individuals in the EPIC-Norfolk study were analyzed for MLH1 gene promoter methylation and microsatellite instability (MSI).

N-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study.

Background: Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. Several NOCs are potential human carcinogens, including N-nitrosodimethylamine (NDMA), but evidence from population studies is inconsistent.

Objective: We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, United Kingdom, study.

SMAD7 and MGMT genotype variants and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study.

Purpose: The SMAD7 gene was recently identified to be associated with colorectal cancer risk. Smad7 protein is a known inhibitor of TGF-β signalling pathway which has a prominent role in tumorigenesis. MGMT gene regulates the direct damage reversal repair pathway, preventing DNA damage and potential cancer development.

Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study.

Background: BRAF and K-ras proto-oncogenes encode components of the ERK signalling pathway and are frequently mutated in colorectal cancer. This study investigates the associations between BRAF and K-ras mutations and clinicopathological, lifestyle and dietary factors in colorectal cancers.

Methods: 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for BRAF and K-ras mutations.

Lifestyle factors and p53 mutation patterns in colorectal cancer patients in the EPIC-Norfolk study.

The tumour suppressor p53 is one of the most commonly altered genes in colorectal cancer (CRC) development. Genetic alterations in p53 may therefore be associated with postulated lifestyle risk factors for CRC, such as red meat consumption. In the European Prospective Investigation into Cancer and Nutrition-Norfolk study, we examined whether detailed estimates of dietary and lifestyle factors measured at baseline related to later development of p53 mutations in CRCs.

MGMT Ile143Val polymorphism, dietary factors and the risk of breast, colorectal and prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study.

O(6)-Methylguanine-DNA methyltransferase (MGMT) repairs DNA damage caused by alkylating agents including N-nitroso compounds from diet. MGMT Ile143Val polymorphism may lead to less DNA damage repair and increased cancer risk depending on the environmental exposures. We investigated interactions between dietary factors and the MGMT Ile143Val polymorphism in relation to breast, colorectal and prostate cancer risk.

Comparing 3 dietary pattern methods--cluster analysis, factor analysis, and index analysis--With colorectal cancer risk: The NIH-AARP Diet and Health Study.

The authors compared dietary pattern methods-cluster analysis, factor analysis, and index analysis-with colorectal cancer risk in the National Institutes of Health (NIH)-AARP Diet and Health Study (n = 492,306). Data from a 124-item food frequency questionnaire (1995-1996) were used to identify 4 clusters for men (3 clusters for women), 3 factors, and 4 indexes. Comparisons were made with adjusted relative risks and 95% confidence intervals, distributions of individuals in clusters by quintile of factor and index scores, and health behavior characteristics.

Baseline alcohol consumption, type of alcoholic beverage and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition-Norfolk study.

Excessive alcohol consumption has been associated with increased risk of colorectal cancer (CRC). However, the effect of modest alcohol consumption or of particular types of beverages on CRC risk remains unclear. We examined whether consumption of total alcohol or specific types of alcoholic beverages relate to overall or site-specific CRC risk in a prospective population study of 24,244 participants and 407 incident CRC cases after 11 years of follow-up.

APOE genotype, lipids, and coronary heart disease risk: a prospective population study.

Background: The risk of coronary heart disease (CHD) may be related to genetic mutations in the production of apolipoprotein E via alterations to the metabolism of CHD-related blood lipids such as low-density lipoprotein cholesterol and triglycerides.

Methods: The relationship between APOE genotype (*E3/*E3, *E3/*E4, *E2/*E3, *E4/*E4, *E2/*E4, and *E2/*E2) and fatal and nonfatal CHD was examined among 10 035 men and 12 134 women, aged 440 to 79 years, from the Norfolk, England, arm of the European Prospective Into Nutrition and Cancer Study (1993-2007). During an average of 11 years of follow-up, 2712 CHD events were documented.

A combined healthy lifestyle score and risk of pancreatic cancer in a large cohort study.

Background: Smoking, alcohol use, diet, body mass index (calculated as weight in kilograms divided by height in meters squared), and physical activity have been studied independently in relation to pancreatic cancer. We generated a healthy lifestyle score to investigate their joint effect on risk of pancreatic cancer.

Methods: In the prospective National Institutes of Health-AARP Diet and Health Study, a total of 450 416 participants aged 50 to 71 years completed the baseline food frequency questionnaire (1995-1996) eliciting diet and lifestyle information and were followed up through December 31, 2003.

Is bowel habit linked to colorectal cancer? - Results from the EPIC-Norfolk study.

Bowel habit has been associated with colorectal carcinogenesis; however, findings from epidemiologic studies have been limited and inconsistent. The aim of this study was to explore the association between bowel habit and colorectal cancer (CRC) risk in the UK-Norfolk arm of the European Prospective Investigation Into Cancer and Nutrition (EPIC-Norfolk), a study of 25,663 men and women aged 45-79 years at entry. Having loose stools compared to soft stools was associated with an approximately 3-fold increased risk, and the association remained significant when lifestyle factors and bowel habit variables were included as covariates in the model (odds ratio (OR), 2.

Dietary patterns as identified by factor analysis and colorectal cancer among middle-aged Americans.

Background: Although diet has long been suspected as an etiological factor for colorectal cancer, studies of single foods and nutrients have provided inconsistent results.

Objective: We used factor analysis methods to study associations between dietary patterns and colorectal cancer in middle-aged Americans.

Design: Diet was assessed among 293,615 men and 198,767 women in the National Institutes of Health-AARP Diet and Health Study.

Mediterranean dietary pattern and prediction of all-cause mortality in a US population: results from the NIH-AARP Diet and Health Study.

Background: The Mediterranean diet has been suggested to play a beneficial role for health and longevity. However, to our knowledge, no prospective US study has investigated the Mediterranean dietary pattern in relation to mortality.

Methods: Study participants included 214,284 men and 166,012 women in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study.

Calcium, dairy foods, and risk of incident and fatal prostate cancer: the NIH-AARP Diet and Health Study.

Calcium and dairy foods in relation to prostate cancer were examined in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study (1995/1996-2001). Diet was assessed with a food frequency questionnaire at baseline. Multivariate relative risks and 95% confidence intervals were estimated by Cox regression.

A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland).

High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 50-69 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire.

Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study.

NADP(H):quinone oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with colorectal neoplasia because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with colorectal carcinogenesis. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal colorectal adenomas in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought.

MTHFR (C677T and A1298C) polymorphisms and risk of sporadic distal colorectal adenoma in the UK Flexible Sigmoidoscopy Screening Trial (United Kingdom).

Objective: The purpose of this study was to further evaluate the role of low activity MTHFR variants as well as to explore interactive effects between alcoholic drink consumption and MTHFR variants and risk of distal colorectal adenomatous polyps.

Methods: We examined the relationship between MTHFR C677T and A1298C gene polymorphisms and risk of distal adenomas in one of the largest case control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening Trial (UKFSS).

Results: Investigation of the effect of the MTHFR C677T polymorphism in this large UKFSS study revealed no overall association on adenoma risk (P>0.