Diet, physical activity, and body size associations with rectal tumor mutations and epigenetic changes.

Diet and lifestyle factors have been inconsistently associated with rectal tumors. It is possible that evaluation of specific tumor markers with these factors may help clarify these associations. In this study, we examine energy contributing nutrients, dietary fiber, BMI (kg/m2), and long-term physical activity with TP53 mutations, KRAS2 mutations, and CpG Island Methylator Phenotype (CIMP) in 750 population-based cases of rectal cancer compared to healthy controls.

Analysis of dietary patterns in epidemiological research.

Dietary patterns have been used to summarize diet consumption and to evaluate how diet is associated with diseases in epidemiological research. However, there are many issues surrounding both the use and interpretation of dietary patterns. These issues include how to collect, summarize, and create dietary patterns, as well as how to interpret the results.

Associations among body mass index, waist circumference, and health indicators in American Indian and Alaska Native adults.

Purpose: Little is known about obesity-related health issues among American Indian and Alaska Native (AIAN) populations.

Approach: A large cohort of AIAN people was assembled to evaluate factors associated with health.

Setting: The study was conducted in Alaska and on the Navajo Nation.

Increased risk of colon cancer associated with a genetic polymorphism of SMAD7.

Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer. We evaluated single nucleotide polymorphisms (SNP) in the SMAD7 gene, including rs4939827, rs12953717, and rs4464148, previously identified from GWAS in a large population-based case-control study of colon cancer. We observed that rs12953717 was associated with a statistically significant increased risk of colon cancer [odds ratio, 1.

Assessing tumor mutations to gain insight into base excision repair sequence polymorphisms and smoking in colon cancer.

DNA repair enzymes function in major pathways to reverse DNA damage, including base excision repair (BER). Missense polymorphisms in BER repair genes may contribute to differences in DNA repair capacity, specific mutations, and susceptibility to cancer in the presence of exposure to carcinogens such as cigarette smoking. In a study of 1,604 incident colon cancer cases and 1,969 matched population-based controls genotyped for BER variants OGG1 (S326C) and XRCC1 (R194W, R280H, and R399Q), we found no associations with colon cancer overall.

Convergence of hormones, inflammation, and energy-related factors: a novel pathway of cancer etiology.

Colorectal cancer (CRC) is a multifactorial disease with several hypothesized etiologic factors including inflammatory processes; hormones such as estrogen, androgen, and insulin; and energy-related factors. We present evidence that integrates these elements in a pathway we call the convergence of hormones, inflammation, and energy-related factors (CHIEF). First, given the physiology of the gut, substantial epidemiologic and molecular data support the hypothesis that activation of innate immunity in the normal gut mucosa by various environmental agents (commensal bacteria, dietary antigens, mucosal irritants, pathogens) and endogenous factors such as estrogen, androgens, and insulin levels provokes basal inflammation as an underlying factor of the association of insulin, estrogen, and energy-related factors with CRC.

Serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 in relation to breast cancer among Hispanic and white, non-Hispanic women in the US Southwest.

Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been positively associated with breast cancer, especially among premenopausal women. Hispanic women have lower levels of IGF-1 and IGFBP-3 than non-Hispanic white (NHW) women, although no studies have adequately assessed the relationship among IGF-1, IGFBP-3, and breast cancer in Hispanic women. We investigated the association among IGF-1, IGFBP-3, and breast cancer within a subset of participants (n = 184 cases, 522 controls) of a population-based case-control study of women living in the U.

Characteristics associated with mammography screening among both Hispanic and non-Hispanic white women.

Aims: This study explores whether certain population characteristics are associated with adherence to mammography screening guidelines among Hispanic and non-Hispanic white (NHW) women living in the southwestern United States.

Methods: Participants in a population-based study (4-Corners' Breast Cancer Study) included in this analysis were 790 Hispanic women and 1,441 NHW women. Multivariate logistic regression was used to compute the ethnic-specific adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association of the outcome variable (adherent vs.

Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk.

Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-alpha hydroxylase (CYP27B1) and vitamin D deactivating enzyme 24-alpha hydroxylase (CYP24A1). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1, identified by resequencing the gene in 32 Caucasian samples, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in VDR.

Microsatellite instability and survival in rectal cancer.

Objective: High levels of microsatellite instability (MSI-H) have been associated in many studies with improved prognosis in colon cancer. Very few studies have evaluated the effect of MSI-H on rectal cancer survival. We assessed MSI-H and other genetic and epigenetic changes on survival of 990 individuals diagnosed with first primary rectal cancer.

Family health history and health behaviors in Alaska native and American Indian people.

Background: Family history of diseases among American Indian and Alaska Native (AIAN) people may influence health.

Methods: We examine the prevalence of family health history among a cohort of AIAN people (n= 10,374) enrolled in the Education and Research Towards Health (EARTH) Study. We evaluate the association between having a positive family history and health behaviors to determine if those reporting a family history were more likely to report lifestyles that put them at risk of developing these health conditions.

Physical activity patterns of American Indian and Alaskan Native people living in Alaska and the Southwestern United States.

Purpose: Assessment of self-reported physical activity (PA) and effects on health measures.

Design: Cross-sectional analysis of baseline data from a cohort study.

Setting: Education and Research Towards Health study participants from Alaska and the Southwestern United States enrolled from 2004 to 2007.

MSH6 G39E polymorphism and CpG island methylator phenotype in colon cancer.

The MSH6 G39E germline polymorphism is not associated with an increased risk of either microsatellite stable or unstable sporadic colorectal cancer. Other than microsatellite instability, however, most genetic and epigenetic changes of tumors associated with this common variant have not been studied. The objective of our investigation was to evaluate associations between the MSH6 G39E (116G>A) polymorphism and CpG island methylator phenotype (CIMP) and BRAF V600E mutations in tumors from a sample of 1048 individuals with colon cancer and 1964 controls from Utah, Northern California, and Minnesota.

A comparison of colon and rectal somatic DNA alterations.

Purpose: Differences in acquired mutations in colon and rectal tumors may account for differences in risk factors. In this study, we examined similarities and differences in somatic alterations in colon and rectal tumors.

Methods: Cases were identified from two large population-based case-control studies of colon cancer and rectal cancer.

Tumor markers and rectal cancer: support for an inflammation-related pathway.

Inflammation may be a key element in the etiology of colorectal cancer. In our study, we examine associations between factors related to inflammation and specific rectal cancer mutations. A population-based study of 750 rectal cancer cases with interview and tumor DNA were compared to 1,205 population-based controls.

Somatic alterations, metabolizing genes and smoking in rectal cancer.

Cigarette smoking has been identified as a risk factor for rectal cancer. Our investigation evaluates associations between active and passive smoking and TP53, KRAS2, and BRAF V600E mutations, microsatellite instability (MSI), and CpG Island Methylator Phenotype (CIMP) in rectal tumors. We examine how genetic variants of GSTM1 and NAT2 alter these associations in a population-based, case-control study of 750 incident rectal cancer cases and 1,201 controls.

Factors associated with response to a follow-up postal questionnaire in a cohort of American Indians.

Objective: The aim of the study was to collect pilot data on response rates to a follow-up postal questionnaire in a cohort of American Indians living in the Southwestern United States. We tested the effect of questionnaire length on response.

Methods: Cohort members were American Indian adults aged 18 and over who completed the baseline study visit.

Physical activity and risk of recurrence and mortality in breast cancer survivors: findings from the LACE study.

Introduction: Identifying modifiable factors that reduce the risk of recurrence and improve survival in breast cancer survivors is a pressing concern. The purpose of this study was to examine the association of physical activity following diagnosis and treatment with the risk of breast cancer recurrence and mortality and all-cause mortality in women with early-stage breast cancer.

Materials And Methods: The sample consisted of 1,970 women from the Life After Cancer Epidemiology study, a prospective investigation of behavioral risk factors and health outcomes.

Colorectal cancer risk prediction tool for white men and women without known susceptibility.

Purpose: Given the high incidence of colorectal cancer (CRC), and the availability of procedures that can detect disease and remove precancerous lesions, there is a need for a model that estimates the probability of developing CRC across various age intervals and risk factor profiles.

Methods: The development of separate CRC absolute risk models for men and women included estimating relative risks and attributable risk parameters from population-based case-control data separately for proximal, distal, and rectal cancer and combining these estimates with baseline age-specific cancer hazard rates based on Surveillance, Epidemiology, and End Results (SEER) incidence rates and competing mortality risks.

Results: For men, the model included a cancer-negative sigmoidoscopy/colonoscopy in the last 10 years, polyp history in the last 10 years, history of CRC in first-degree relatives, aspirin and nonsteroidal anti-inflammatory drug (NSAID) use, cigarette smoking, body mass index (BMI), current leisure-time vigorous activity, and vegetable consumption.

Dietary patterns and breast cancer recurrence and survival among women with early-stage breast cancer.

Purpose: To determine the association of dietary patterns with cancer recurrence and mortality of early-stage breast cancer survivors.

Patients And Methods: Patients included 1,901 Life After Cancer Epidemiology Study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California Cancer Registry. Diet was assessed at cohort entry using a food frequency questionnaire.

Metabolic syndrome: prevalence among American Indian and Alaska native people living in the southwestern United States and in Alaska.

Background: Metabolic syndrome occurs commonly in the United States. The purpose of this study was to measure the prevalence of metabolic syndrome among American Indian and Alaska Native people.

Methods: We measured the prevalence rates of metabolic syndrome, as defined by the National Cholesterol Education Program, among four groups of American Indian and Alaska Native people aged 20 years and older.

Traditional foods and physical activity patterns and associations with cultural factors in a diverse Alaska Native population.

Objectives: To determine the prevalence of traditional food and physical activity use and associations with cultural factors among 3,830 Alaska Native and American Indian (AN/AI) people enrolled in the Education and Research Towards Health (EARTH) Study in 3 regions of Alaska.

Study Design: Cross-sectional analysis of baseline data from a cohort study.

Methods: Participants (2,323 women and 1,507 men) completed a computer-assisted self-administered questionnaire that included information on diet, physical activity, life-style and cultural factors.

Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways.

Variation in genes associated with serum levels of proteins may be useful for examining specific disease pathways. Using data from a large study of colon cancer, we examine genetic variants in insulin, inflammation, estrogen, metabolizing enzymes, and energy homeostasis genes to explore associations with microsatellite instability (MSI), CpG Island methylator phenotype (CIMP), mutations of p53 in exons 5 through 8, and mutations in codons 12 and 13 of Ki-ras. Insulin-related genes were associated with CIMP-positive and MSI tumors, with the strongest associations among aspirin users.

Genetic variation in calcium-sensing receptor and risk for colon cancer.

Background: Experimental and epidemiologic studies have suggested that high calcium intake is associated with decreased colon cancer risk, yet very limited data are available for candidate genes in the calcium-vitamin D pathway and colon cancer risk. To address this, we evaluated whether calcium-sensing receptor (CASR) single-nucleotide polymorphisms are associated with colon cancer risk. We also examined interactions among CASR, calcium, and vitamin D intake and previously genotyped vitamin D-related genes.

Differences in estrogen receptor subtype according to family history of breast cancer among Hispanic, but not non-Hispanic White women.

Background: Pathologic differences have been reported among breast tumors when comparing ethnic populations. Limited research has been done to evaluate the ethnic-specific relationships between breast cancer risk factors and the pathologic features of breast tumors.

Methods: Given that genetic variation may contribute to ethnic-related etiologic differences in breast cancer, we hypothesized that tumor characteristics differ according to family history of breast cancer among Hispanic and non-Hispanic White (NHW) women.