title: Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: CR-UK Genetic Epidemiology Unit, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
authors: Andrea
authors: A
authors: Mann
authors: Estrid
authors: E
authors: Hogdall
authors: Susan J
authors: SJ
authors: Ramus
authors: Richard A
authors: RA
authors: DiCioccio
authors: Claus
authors: C
authors: Hogdall
authors: Lydia
authors: L
authors: Quaye
authors: Valerie
authors: V
authors: McGuire
authors: Alice S
authors: AS
authors: Whittemore
authors: Mitul
authors: M
authors: Shah
authors: David
authors: D
authors: Greenberg
authors: Douglas F
authors: DF
authors: Easton
authors: Bruce A J
authors: BA
authors: Ponder
authors: Susanne Krüger
authors: SK
authors: Kjaer
authors: Simon A
authors: SA
authors: Gayther
authors: Deborah J
authors: DJ
authors: Thompson
authors: Paul D P
authors: PD
authors: Pharoah
authors: Honglin
authors: H
authors: Song
mesh_terms: D000328:Adult; D053843:DNA Mismatch Repair; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D004812:Epidemiologic Methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D004273:DNA, Neoplasm