Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis

Sambuddha Das,Aditi Bhowmik,Sankar Kumar Ghosh,Sayantan Nath,Yashmin Choudhury

doi:10.1186/s40064-016-1858-5

Abstract

Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mortality around the world. DNA repair genes play a vital role in preventing carcinogenesis by maintaining genomic integrity. Polymorphisms in the nucleotide sequence of DNA repair genes are often reported to be associated with an increased risk for different cancers. The OGG1 gene encodes the enzyme 8-oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA. Several studies report that the OGG1 Ser326Cys polymorphism increases the risk for cancers of the upper aero-digestive and gastrointestinal tract. However, other studies provide evidence that such an association does not exist. A meta-analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the upper aero-digestive and gastrointestinal tract was therefore undertaken in order to resolve this ambiguity. Seventeen studies were recruited for this meta-analysis after screening 58 articles with a total of 5533 cases and 6834 controls for which the odds ratio with 95 % confidence interval was calculated. Begg’s funnel test and Egger’s test were performed for calculating publication bias. Our study reveals an association between OGG1 Ser326Cys polymorphism and cancer susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs CC; odds ratio, OR 1.22; 95 % CI 1.05–1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09–1.70; GG vs CC; OR 1.46; 95 % CI 1.12–1.92). Subgroup analysis based on cancer types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism to the risk for upper aero-digestive and gastrointestinal tract cancers among both the Asian and the Caucasian populations. No risk was however observed for smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys polymorphism may be associated with the increased risk for aero-digestive tract and gastro-intestinal cancers in both Asian and Caucasian populations.

Highlights

Cancer is a multifarious disease characterised by abrupt growth of cells resulting in abnormal regulation of cellcycle progression and division (Sawyers 2004)
Selection criteria Articles for the meta-analysis were selected if they met the following criteria: (1) Studies not prior to 2007 (2) case–control study related to the risk of OGG1 Ser326Cys polymorphism (3) articles written in English (4) studies in which full information about genotype distributions are reported (5) Studies in which genotype distribution of control populations are in accordance with Hardy–Weinberg Equilibrium (P > 0.05) (6) only original research articles excluding reviews, letters and case reports
Summary of included studies In a preliminary search, we identified 58 research articles related to OGG1 Ser326Cys polymorphism and the risk of head and neck, oral, pancreatic, gallbladder, colorectal and gastric cancers

Summary

Introduction

Cancer is a multifarious disease characterised by abrupt growth of cells resulting in abnormal regulation of cellcycle progression and division (Sawyers 2004). Increased levels of 8-oxoG have been reported in the lung DNA of smokers in comparison to those of non-smokers, indicating a clear correlation with tobacco related carcinogenesis. Together the tobacco smoke and its aqueous solution can lead to various aerodigestive and upperdigestive tract cancers (Elahi et al 2002). The human 8-oxoguanine DNA glycosylase (OGG1), encoded by the OGG1 gene localized on chromosome 3p25 has both DNA glycosylase and apurinic or apyrimidinic (AP) lyase activities. It removes the 8-oxoG lesion by slicing the glycosydic bond between the modified base and the sugar moiety, leaving an abasic apurinic/apyrimidinic (AP) site in DNA (Zhou et al 2015)

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