Genes, environment and gene expression in colon tissue: a pathway approach to determining functionality.

Genetic and environmental factors have been shown to work together to alter cancer risk. In this study we evaluate previously identified gene and lifestyle interactions in a candidate pathway that were associated with colon cancer risk to see if these interactions altered gene expression. We analyzed non-tumor RNA-seq data from 144 colon cancer patients who had genotype, recent cigarette smoking, diet, body mass index (BMI), and recent aspirin/non-steroidal anti-inflammatory use data.

Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study.

Purpose: There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women.

Energy homeostasis genes and survival after breast cancer diagnosis: the Breast Cancer Health Disparities Study.

Purpose: The leptin-signaling pathway and other genes involved in energy homeostasis (EH) have been examined in relation to breast cancer risk as well as to obesity. We test the hypothesis that genetic variation in EH genes influences survival after diagnosis with breast cancer and that body mass index (BMI) will modify that risk.

Methods: We evaluated associations between 10 EH genes and survival among 1,186 non-Hispanic white and 1,155 Hispanic/Native American women diagnosed with breast cancer.

Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study.

Background: Obesity and breast cancer risk is multifaceted and genes associated with energy homeostasis may modify this relationship.

Methods: We evaluated 10 genes that have been associated with obesity and energy homeostasis to determine their association with breast cancer risk in Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (1481 cases, 1585 controls) women.

Results: Cholecystokinin (CCK) rs747455 and proopiomelanocortin (POMC) rs6713532 and rs7565877 (for low Indigenous American (IA) ancestry); CCK rs8192472 and neuropeptide Y (NYP) rs16141 and rs14129 (intermediate IA ancestry); and leptin receptor (LEPR) rs11585329 (high IA ancestry) were strongly associated with multiple indicators of body size.

MAPK genes interact with diet and lifestyle factors to alter risk of breast cancer: the Breast Cancer Health Disparities Study.

Mitogen-activated protein kinases (MAPK) are integration points for multiple biochemical signals. We evaluated 13 MAPK genes with breast cancer risk and determined if diet and lifestyle factors mediated risk. Data from 3 population-based case-control studies conducted in Southwestern United States, California, and Mexico included 4183 controls and 3592 cases.

The influence of the CHIEF pathway on colorectal cancer-specific mortality.

Many components of the CHIEF (Convergence of Hormones, Inflammation, and Energy Related Factors) pathway could influence survival given their involvement in cell growth, apoptosis, angiogenesis, and tumor invasion stimulation. We used ARTP (Adaptive Rank Truncation Product) to test if genes in the pathway were associated with colorectal cancer-specific mortality. Colon cancer (n = 1555) and rectal cancer (n = 754) cases were followed over five years.

Diet and lifestyle factors modify immune/inflammation response genes to alter breast cancer risk and prognosis: the Breast Cancer Health Disparities Study.

Tumor necrosis factor-α (TNF) and toll-like receptors (TLR) are important mediators of inflammation. We examined 10 of these genes with respect to breast cancer risk and mortality in a genetically admixed population of Hispanic/Native American (NA) (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1585 controls) women. Additionally, we explored if diet and lifestyle factors modified associations with these genes.

A pathway approach to evaluating the association between the CHIEF pathway and risk of colorectal cancer.

Inflammation, hormones and energy-related factors have been associated with colorectal cancer (CRC) and it has been proposed that convergence and interactions of these factors importantly influence CRC risk. We have previously hypothesized that genetic variation in the CHIEF (convergence of hormones, inflammation and energy-related factors) pathway would influence risk of CRC. In this paper, we utilize an Adaptive Rank Truncation Product (ARTP) statistical method to determine the overall pathway significance and then use that method to identify the key elements within the pathway associated with disease risk.

An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer.

Background And Aims: Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk.

Methods: We selected 15 validated SNPs associated with risk of either Crohn's disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design.

CYP19A1 single nucleotide polymorphism associations with CYP19A1, NFκB1, and IL6 gene expression in human normal colon and normal liver samples.

Background: Estrogen is known to decrease the risk of colon cancer in postmenopausal women, and may exert its actions by decreasing interleukin-6 (IL6) production via stabilization of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). Estrogens are biosynthesized by CYP19A1 (aromatase), so it is possible that genetic variations in CYP19A1 influences the risk of colon cancer by altering expression of CYP19A1. Further, studies on gene-gene interactions suggest that single nucleotide polymorphisms in one gene may affect expression of other genes.

Genetic variation in the JAK/STAT/SOCS signaling pathway influences breast cancer-specific mortality through interaction with cigarette smoking and use of aspirin/NSAIDs: the Breast Cancer Health Disparities Study.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in immune function and cell growth; genetic variation in this pathway could influence breast cancer risk. We examined 12 genes in the JAK/STAT/SOCS signaling pathway with breast cancer risk and mortality in an admixed population of Hispanic (2,111 cases, 2,597 controls) and non-Hispanic white (1,481 cases, 1,585 controls) women. Associations were assessed by Indigenous American (IA) ancestry.

Diet and lifestyle factors interact with MAPK genes to influence survival: the Breast Cancer Health Disparities Study.

Introduction: MAPK genes are activated by a variety of factors related to growth factors, hormones, and environmental stress.

Methods: We evaluated associations between 13 MAPK genes and survival among 1,187 nonHispanic White and 1,155 Hispanic/Native American (NA) women diagnosed with breast cancer. We assessed the influence of diet, lifestyle, and genetic ancestry on these associations.

Influence of CHIEF pathway genes on gene expression: a pathway approach to functionality.

Background: Candidate pathway approaches in disease association studies often utilize a tagSNP approach to capture genetic variation. In this paper we assess gene expression patterns with SNPs in genes in the CHIEF pathway to help determine their potential functionality.

Methods: Quantitative real-time RT-PCR was run to determine gene expression of 13 genes in normal colon tissue samples from 82 individuals.

The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study.

The TGF-β signaling pathway regulates cellular proliferation and differentiation. We evaluated genetic variation in this pathway, its association with breast cancer survival, and survival differences by genetic ancestry and self-reported ethnicity. The Breast Cancer Health Disparities Study includes participants from the 4-Corners Breast Cancer Study (n = 1,391 cases) and the San Francisco Bay Area Breast Cancer Study (n = 946 cases) who have been followed for survival.

SEPP1 influences breast cancer risk among women with greater native american ancestry: the breast cancer health disparities study.

Selenoproteins are a class of proteins containing a selenocysteine residue, many of which have been shown to have redox functions, acting as antioxidants to decrease oxidative stress. Selenoproteins have previously been associated with risk of various cancers and redox-related diseases. In this study we evaluated possible associations between breast cancer risk and survival and single nucleotide polymorphisms (SNPs) in the selenoprotein genes GPX1, GPX2, GPX3, GPX4, SELS, SEP15, SEPN1, SEPP1, SEPW1, TXNRD1, and TXNRD2 among Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women in the Breast Cancer Health Disparities Study.

Lack of correlation between in silico projection of function and quantitative real-time PCR-determined gene expression levels in colon tissue.

There are a number of in silico programs that use algorithms and external web sources to predict the effect of single nucleotide polymorphisms (SNPs). While many of these programs have been shown to predict accurately the effect of SNPs in functional areas of the gene, such as 5' upstream or coding regions, empiric research may be warranted to confirm the functional consequences of SNPs that are predicted to have little to no effect. We compared predictions from FASTSNP (Function Analysis and Selection Tool for Single Nucleotide Polymorphism) and F-SNP (Functional Single Nucleotide Polymorphism) with experimentally derived genotype-phenotype correlations to determine the accuracy of these programs in predicting SNP functionality.

Associations with growth factor genes (FGF1, FGF2, PDGFB, FGFR2, NRG2, EGF, ERBB2) with breast cancer risk and survival: the Breast Cancer Health Disparities Study.

Growth factors (GF) stimulate cell proliferation through binding to cell membrane receptors and are thought to be involved in cancer risk and survival. We examined how genetic variation in epidermal growth factor (EGF), neuregulin 2 (NRG2), ERBB2 (HER2/neu), fibroblast growth factors 1 and 2 (FGF1 and FGF2) and its receptor 2 (FGFR2), and platelet-derived growth factor B (PDGFB) independently and collectively influence breast cancer risk and survival. We analyzed data from the Breast Cancer Health Disparities Study which includes Hispanic (2,111 cases, 2,597 controls) and non-Hispanic white (1,481 cases, 1,586 controls) women.

Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer.

Mitogen-activated protein kinase (MAPK) pathways regulate cellular functions including cell proliferation, differentiation, migration, and apoptosis. Associations between genes in the DUSP, ERK1/2, JNK, and p38 MAPK-signaling pathways and dietary factors associated with growth factors, inflammation, and oxidative stress and risk of colon and rectal cancer were evaluated. Data include colon cases (n = 1555) and controls (n = 1956) and rectal cases (n = 754) and controls (n = 959).

Angiogenesis genes, dietary oxidative balance and breast cancer risk and progression: the Breast Cancer Health Disparities Study.

Angiogenesis is essential for tumor development and progression. Genetic variation in angiogenesis-related genes may influence breast carcinogenesis. We evaluated dietary factors associated with oxidative balance, DDIT4 (one SNP), FLT1 (35 SNPs), HIF1A (four SNPs), KDR (19 SNPs), MPO (one SNP), NOS2A (15 SNPs), TEK (40 SNPs) and VEGFA (eight SNPs) and breast cancer risk among Hispanic (2,111 cases and 2,597 controls) and non-Hispanic white (1,481 cases and 1,586 controls) women in the Breast Cancer Health Disparities Study.

VEGFA, FLT1, KDR and colorectal cancer: assessment of disease risk, tumor molecular phenotype, and survival.

Angiogenesis is essential for tumor progression. Vascular endothelial growth factor (VEGFA) and its receptors 1 (FLT1) and 2 (KDR), have been identified as major mediators of this process. We hypothesized that genetic variation in FLT1 (38 SNPs), KDR (22 SNPS), and VEGFA (11 SNPs) would be associated with colon and rectal cancer development and survival.

Matrix metalloproteinase genes are associated with breast cancer risk and survival: the Breast Cancer Health Disparities Study.

Matrix metalloproteinases (MMPs) contribute to cancer through their involvement in cancer invasion and metastasis. We evaluated genetic variation in MMP1 (9 SNPs), MMP2 (8 SNPs), MMP3 (4 SNPs), and MMP9 (3 SNPs) and breast cancer risk among Hispanic (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women in the Breast Cancer Health Disparities Study. Ancestral informative markers (n = 104) were assessed to determine Native American (NA) ancestry.

Telomere length, telomere-related genes, and breast cancer risk: the breast cancer health disparities study.

Telomeres are involved in maintaining genomic stability. Previous studies have linked both telomere length (TL) and telomere-related genes with cancer. We evaluated associations between telomere-related genes, TL, and breast cancer risk in an admixed population of US non-Hispanic white (1,481 cases, 1,586 controls) and U.

Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study.

Background: Telomeres cap the ends of chromosomes and help maintain genomic stability and integrity. Telomere length (TL) has been linked to a number of diseases, including a variety of cancers; however, the association between TL and risk for colorectal cancer is unclear.

Methods: We investigate the association between genetic, diet, and lifestyle factors and TL and the association between TL and colorectal cancer using data from a population-based case-control study of colon (249 cases and 371 controls) and rectal cancer (276 cases and 372 controls) conducted in Utah.

MAP kinase genes and colon and rectal cancer.

Mitogen-activated protein kinase (MAPK) pathways regulate many cellular functions including cell proliferation, differentiation, migration and apoptosis. We evaluate genetic variation in the c-Jun-N-terminal kinases, p38, and extracellular regulated kinases 1/2 MAPK-signaling pathways and colon and rectal cancer risk using data from population-based case-control studies (colon: n = 1555 cases, 1956 controls; rectal: n = 754 cases, 959 controls). We assess 19 genes (DUSP1, DUSP2, DUSP4, DUSP6, DUSP7, MAP2K1, MAP3K1, MAP3K2, MAP3K3, MAP3K7, MAP3K9, MAP3K10, MAP3K11, MAPK1, MAPK3, MAPK8, MAPK12, MAPK14 and RAF1).

PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer.

Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators.