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Possible association between a genetic polymorphism at 8q24 and risk of upper gastrointestinal cancer.

ABSTRACT: Over recent years, genome-wide association studies have contributed to our understanding of genetic susceptibility to sporadic cancer. In this study, we assessed the association between upper gastrointestinal cancer risk and four genome-wide association studies-identified single nucleotide polymorphisms (SNPs), implicated earlier in prostate and colorectal cancer susceptibility. Genotyping for each SNP was performed in two independent Caucasian population-based case-control studies. The first study comprised 290 gastric cancer cases and 374 controls. The second study included 185 noncardia gastric cancers, 123 cardia cancers, 158 oesophageal cancers and 209 controls. Odds ratios (ORs) were computed from logistic models and adjusted for potential confounding variables. An inverse association was observed between the SNP rs1447295, located at 8q24, and gastric cancer risk in the first study population (OR=0.63; 95% confidence interval: 0.41-0.97). A positive association was observed for the same SNP and oesophageal squamous cell carcinoma in the second study population (OR=7.43; 95% confidence interval: 1.37-49.98). No significant associations were detected in either study for the three remaining SNPs (rs6983297, rs10505477 and rs719725). Our data represent novel findings on heritable susceptibility to gastric and oesophageal cancer and warrant validation in additional populations.

SUBMITTER: Lochhead P

PROVIDER: S-EPMC3020097 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Possible association between a genetic polymorphism at 8q24 and risk of upper gastrointestinal cancer.

Lochhead Paul P Ng Michael T H MT Hold Georgina L GL Rabkin Charles S CS Vaughan Thomas L TL Gammon Marilie D MD Risch Harvey A HA Lissowska Jolanta J Mukhopadhya Indrani I Chow Wong-Ho WH El-Omar Emad M EM

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 20110101 1

Over recent years, genome-wide association studies have contributed to our understanding of genetic susceptibility to sporadic cancer. In this study, we assessed the association between upper gastrointestinal cancer risk and four genome-wide association studies-identified single nucleotide polymorphisms (SNPs), implicated earlier in prostate and colorectal cancer susceptibility. Genotyping for each SNP was performed in two independent Caucasian population-based case-control studies. The first st ...[more]

PMID: 21102338

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Project description:BackgroundGastrointestinal cancer, such as gastric, colon and rectal cancer, is a major medical and economic burden worldwide. However, the exact mechanism of gastrointestinal cancer development still remains unclear. RAS genes have been elucidated as major participants in the development and progression of a series of human tumours and the single nucleotide polymorphism at H-RAS cDNA position 81 was demonstrated to contribute to the risks of bladder, oral and thyroid carcinoma. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to gastrointestinal cancer as well, and we conducted this study to test the hypothesis in Chinese population.MethodsA population based case-control study, including 296 cases with gastrointestinal cancer and 448 healthy controls selected from a Chinese population was conducted. H-RAS T81C polymorphism was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay.ResultsIn the healthy controls, the TT, TC and CC genotypes frequencies of H-RAS T81C polymorphism, were 79.24%, 19.87% and 0.89%, respectively, and the C allele frequency was 10.83%. Compared with TT genotype, the TC genotype was significantly associated with an increased risk of gastric cancer (adjusted OR = 3.67, 95%CI = 2.21-6.08), while the CC genotype showed an increased risk as well (adjusted OR = 3.29, 95%CI = 0.54-19.86), but it was not statistically significant. In contrast, the frequency of TC genotype was not significantly increased in colon cancer and rectal cancer patients. Further analysis was performed by combining TC and CC genotypes compared against TT genotype. As a result, a statistically significant risk with adjusted OR of 3.65 (95%CI, 2.22-6.00) was found in gastric cancer, while no significant association of H-RAS T81C polymorphism with colon cancer and rectal cancer was observed.ConclusionThese findings indicate, for the first time, that there is an H-RAS T81C polymorphism existing in Chinese population, and this SNP might be a low penetrance gene predisposition factor for gastric cancer.

Dataset Information

Possible association between a genetic polymorphism at 8q24 and risk of upper gastrointestinal cancer.

Publications

Possible association between a genetic polymorphism at 8q24 and risk of upper gastrointestinal cancer.

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