Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients

Aims: Inherited genetic factors may help partially explain variability of survival length amongst ovarian cancer patients. Of particular interest are genes involved in DNA repair, specifically those involved in mismatch repair (MMR). The aim of this study was to investigate the possible association between the common variants in MMR genes and invasive ovarian cancer overall survival. Method/results: We examined associations between 44 variants that tag the known common variants (minor allele frequency ≥0.05) in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) and survival of invasive ovarian cancer patients in three case-control studies from United Kingdom (UK), Denmark and California of United States of America (USA). DNA from up to 1495 women were genotyped. The genotypes of each polymorphism were tested for association with survival using Cox regression analysis stratified by study. A nominally significant association (P = 0.04) between genotype and ovarian cancer survival was observed for rs2228006 in PMS2. The per-rare allele hazard ratio (HR 95%CI) was 0.84 (0.71-0.99), however, it was not significant after adjusting for multiple covariants (P = 0.47). When the analyses were restricted to serous type ovarian cancer, two SNPs showed marginal significant associations; the per-rare allele HR was 1.3 (1.05-1.6) (P = 0.02) for rs1799977 in MLH1 and 1.4 (1.03-1.9) (P = 0.04) for rs6151662 in MSH3. Neither was significant after adjusting for multiple covariants. Conclusion: It is unlikely that common variants in the MMR pathways examined have moderate effects on survival after diagnosis with ovarian cancer. Much larger studies would be needed to exclude common variants with small effects.