, Volume 21, Issue 2, pp 313-321
Date: 19 Nov 2009

A comprehensive analysis of common genetic variation in MUC1, MUC5AC, MUC6 genes and risk of stomach cancer

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Abstract

Objective

MUC1, MUC5AC, and MUC6 are main constituents of the mucus barrier in the stomach, which protects the underlying epithelium from acid, proteases, mechanical trauma, and pathogenic microorganisms. Accumulating evidence implicates potential roles of MUC1, MUC5AC, and MUC6 genetic variation in the development of stomach cancer.

Methods

We evaluated the relationship between common genetic variations in these genes and stomach cancer risk, using an LD-based tagSNP approach in a population-based case–control study conducted in Warsaw, Poland, during 1994–1996. We genotyped 6, 8, and 14 tagSNPs in MUC1, MUC5AC, and MUC6 genes, respectively, among 273 cases newly diagnosed with stomach cancer and 377 controls.

Results

Each of the six tagSNPs tested across the MUC1 region showed statistically significant associations with an increased risk of stomach cancer. Carriers of the haplotype ACTAA rare alleles of rs4971052, rs4276913, rs4971088, rs4971092, and rs4072037 had a nearly doubled risk (OR = 1.93, 95% CI = 1.49–2.48) compared to the referent haplotype GTAAG. Out of the eight tagSNPs across MUC5AC region, only minor allele of rs868903 was significantly associated with an increased risk of stomach cancer (OR = 1.80, 95% CI = 1.22–2.63).

Conclusions

Overall, our data provide evidence that some common variations in MUC1 and MUC5AC genes contribute to an elevated risk of stomach cancer. Further studies are needed to confirm these novel findings.