Integrated analysis of genome-wide copy number alterations and gene expression in microsatellite stable, CpG island methylator phenotype-negative colon cancer.

Microsatellite stable (MSS), CpG island methylator phenotype (CIMP)-negative colorectal tumors, the most prevalent molecular subtype of colorectal cancer, are associated with extensive copy number alteration (CNA) events and aneuploidy. We report on the identification of characteristic recurrent CNA (with frequency >25%) events and associated gene expression profiles for a total of 40 paired tumor and adjacent normal colon tissues using genome-wide microarrays. We observed recurrent CNAs, namely gains at 1q, 7p, 7q, 8p12-11, 8q, 12p13, 13q, 20p, 20q, Xp, and Xq and losses at 1p36, 1p31, 1p21, 4p15-12, 4q12-35, 5q21-22, 6q26, 8p, 14q, 15q11-12, 17p, 18p, 18q, 21q21-22, and 22q.

Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women.

Genome-wide association studies have identified common genetic variants that can contribute specifically to the risk of abdominal adiposity, as measured by waist circumference or waist-to-hip ratio. However, it is unknown whether these genetic risk factors affect relative body fat distribution in the abdominal visceral and subcutaneous compartments. The association between imaging-based abdominal fat mass and waist-size risk variants in the FTO, LEPR, LYPLAL1, MSRA, NRXN3, and TFAP2B genes was investigated.

cis-Expression QTL analysis of established colorectal cancer risk variants in colon tumors and adjacent normal tissue.

Genome-wide association studies (GWAS) have identified 19 risk variants associated with colorectal cancer. As most of these risk variants reside outside the coding regions of genes, we conducted cis-expression quantitative trait loci (cis-eQTL) analyses to investigate possible regulatory functions on the expression of neighboring genes. Forty microsatellite stable and CpG island methylator phenotype-negative colorectal tumors and paired adjacent normal colon tissues were used for genome-wide SNP and gene expression profiling.

Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies.

Background: Diabetes has been positively associated with the risk of colorectal cancer. This study investigated whether recently established risk variants for diabetes also have effects on colorectal cancer.

Methods: 19 single nucleotide repeats (SNPs) associated with type 2 diabetes in genome-wide association studies were tested in a case-control study of 2011 colorectal cancer cases and 6049 controls nested in the Multiethnic Cohort study as part of the Population Architecture using Genomics and Epidemiology (PAGE) initiative.

Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer.

Context: Cyclin D1 (CCND1) is a key cell cycle regulatory protein, the overexpression of which is often found in human tumors and is associated with cell proliferation and poor prognosis. A common adenine-to-guanine substitution polymorphism (A870G) in the CCND1 gene results in an altered messenger RNA transcript and a longer-life protein, which are preferentially encoded by the A allele.

Objective: To test the overall and stage-specific associations of the CCND1 870A allele with colorectal cancer.

Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk.

N-Nitroso compounds are suspected colorectal cancer (CRC) carcinogens to which individuals on a diet high in red meat (RM) may be particularly exposed. Many of these compounds undergo alpha-hydroxylation by CYP2E1 to form DNA adducts. The gene coding for this enzyme is polymorphic and thus may constitute a susceptibility factor for CRC.

Well-done red meat, metabolic phenotypes and colorectal cancer in Hawaii.

Heterocyclic amines (HAAs) and polycyclic hydrocarbons are suspected colorectal cancer (CRC) carcinogens that are found in well-done meat. They require metabolic activation by phase I enzymes, such as the smoking-inducible CYP1A isoenzymes. N-acetyltransferase 2 (NAT2) also play a role in the further activation of HAAs.

B-vitamin intake, metabolic genes, and colorectal cancer risk (United States).

Objective: This population-based case-control study was designed to investigate the interrelationships between polymorphisms in the methylenetetrahydrofolate (MTHFR C677T and A1298C) gene and other genes (MTR A2756G; MTRR A66G and CBS 844ins68), intake of B-vitamins and colorectal cancer risk (CRC).

Methods: We interviewed 727 CRC cases of Japanese, Caucasian, or Native Hawaiian origin and 727 controls matched on sex, age, and ethnicity.

Results: Compared to the homozygous wild-type genotype, the odds ratios for subjects with one or two MTHFR 677T variant alleles were 0.

Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk.

Oxidative stress may be one mechanism by which tobacco smoke causes lung cancer. A common oxidative damage to DNA is the highly mutagenic 7,8-dihydro-8-oxoguanine adduct, which can be repaired by 8-oxoguanine glycosylase I (OGG1). A Ser326Cys substitution polymorphism in the hOGG1 gene has been suggested, based on in vitro data, to reduce the activity of the enzyme.

Association of a common polymorphism in the human GH1 gene with colorectal neoplasia.

Background: Growth hormone (GH) may be associated with the development of colorectal tumors directly and/or indirectly via an increased plasma level of insulin-like growth factor-I (IGF-I), which has been associated with colorectal cancer risk. Because a T-to-A polymorphism in the human GH1 gene at position 1663 is putatively associated with lower levels of GH and IGF-I, we investigated the relationship of this polymorphism to the risk of colorectal neoplasia.

Methods: We analyzed data from two case-control studies conducted in Hawaii: a population-based study of 535 case patients with colorectal adenocarcinoma and 650 control subjects and a sigmoidoscopy screening-based study with 139 case patients with adenoma and 202 control subjects.