Genetic Susceptibility to Cancer

Abstract

Context-Continuing advances in genotyping technologies and the inclusion of DNA collection in observational studies have resulted in an increasing number of genetic association studies.Objective-To evaluate the overall progress and contribution of candidate gene association studies to current understanding of the genetic susceptibility to cancer.Data Sources-We systematically examined the results of meta-and pooled analyses for genetic polymorphisms and cancer risk published through March 2008.Study Selection-We identified 161 meta-and pooled analyses, encompassing 18 cancer sites and 99 genes. Analyses had to meet the following criteria: 1) at least 500 cases, 2) cancer risk as outcome, 3) not focused on HLA genetic markers, and 4) published in English.Data Extraction-Information on cancer site, gene name, variant, point estimate and 95% confidence interval, allelic frequency, number of studies and cases, tests of study heterogeneity and publication bias were extracted by one investigator and reviewed by other investigators.Results-These 161 analyses evaluated 344 gene-variant/cancer associations and included on average 7.3 studies and 3,551 cases (range: 508-19,729 cases) per investigated association. The summary OR for 98 (28%) statistically significant associations (p-value <0.05) were further

Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer

“…The incidence of the GSTM1-null and the GSTT1-null genotype in our population was 46% and 17%, respectively, which is comparable with the published literature for Caucasians (50% and 20%, respectively) (Dong et al , 2008). Our study showed that the GSTM1-null genotype was positively related with the presence of moderate–severe SOS, making it an independent risk factor for the development of SOS.…”

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

“…Additionally, in an Italian study evaluating 790 CG patients and 202 healthy controls, the TT genotype was associated with an increased risk of GC with ORs of 1.52 (log-additive model of inheritance) and 2.35 (codominant model of inheritance) [ 140 ]. Similar results were found in a study of genetic susceptibility to cancer involving GC samples ( n = 2727), where MTHFR C677T was associated with GC (TT vs. CT + CC; OR: 1.52, 95% CI: 1.31–1.77, p -value = 4.9 × 10 −8 ) [ 141 ].…”

Genome-Wide Meta-Analysis of Homocysteine and Methionine Metabolism Identifies Five One Carbon Metabolism Loci and a Novel Association of ALDH1L1 with Ischemic Stroke

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“…Elevated tHcy has long been associated with increased risk for stroke and cardiovascular disease but to date functional evidence for the driving genetic forces behind elevated tHcy levels have only been attributable, in part, to dysfunction in the methylenetetrahydrofolate reductase gene ( MTHFR [MIM 607093]) and CBS genes [15] – [18] . MTHFR , which also participates in the FOCM pathway, is tightly related to all the genes products identified in our study and has been implicated in susceptibility to vascular disease, neural tube defects, colon cancer and acute leukemia [19] – [24] . It is interesting to note that a prior GWAS in the individual FHS and VISP cohorts or in a meta-analysis yielded no significant results for baseline tHcy alone.…”