Matrix metalloproteinase9 gene polymorphisms are associated with a multiple family history of gastric cancer.

Abstract

A family history of gastric cancer (GC) is a well-known risk factor of GC. Genetic variations in genes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been related to the risk of GC, but their association with familial background is not clear. We investigated whether individuals with a multiple family history of GC have more risk genotypes of MMP/TIMP genes. We genotyped ten common functional polymorphisms of MMP/TIMP genes in 4427 individuals aged 35-69years without a history of GC who were enrolled in the Japan Multi-institutional Collaborative Cohort Study. Individuals who have two or more first-degree relatives (parents and siblings) with GC were categorized as having a multiple family history. Odds ratios (ORs) for multiple family history compared with no family history were calculated. MMP9 279QQ (rs17576) was more frequently observed in individuals whose both parents had a history of GC (n=23) and in individuals for whom one parent and their sibling(s) had a history of GC (n=36) compared with those with no family history (n=3816) [30.4% vs 11.6%, OR 4.34, 95% confidence interval (CI) 1.45-13.03 and 16.7% vs 11.6%, OR 2.26, 95% CI 0.81-6.27 after adjustment for age, sex, and current smoking]. The population attributable fraction was 38.1%. The haplotype MMP9-1562C/279Q/668Q was more frequently observed in individuals whose both parents had a history of GC and in individuals for whom one parent and their sibling(s) had a history of GC compared with those with no family history (OR 3.35, 95% CI 0.75-14.96 and OR 3.51, 95% CI 1.35-9.15 respectively). MMP9 polymorphisms were associated with a multiple family history of GC. Screening for these genotypes together with familial background may help us to identify individuals at an increased risk of GC.