title: Ovarian cancer risk is associated with a common variant in the promoter sequence of the mismatch repair gene MLH1.
abstract: OBJECTIVE
  Inherited mutations in the MLH1 gene are associated with a proportion of families with the hereditary non-polyposis colon cancer syndrome (HNPCC). The cardinal features of the syndrome are a predisposition to colon, endometrial and ovarian cancers. Recently, it has been shown that a non-coding polymorphic variant in MLH1 (G>A nt-93) predisposes to colon and endometrial cancer, but with much reduced penetrance. We sought to establish whether or not this polymorphic variant also predisposes to ovarian cancer.
  
  
  METHODS
  We genotyped 899 women with invasive ovarian cancer and 931 controls for the G>A nt-93 variant.
  
  
  RESULTS
  The presence of the variant was associated with a modest, but highly significant risk of ovarian cancer (OR=1.5; 95% CI 1.3-1.9; p=0.00005). The association was present in cancers of all histologies except clear cell, and in all ethnic groups.
  
  
  CONCLUSIONS
  The G>A nt-93 variant of the MLH1 gene is associated with an increased risk of invasive ovarian cancer.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, ON, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Harley
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.forename: Kathy
authors.initials: K
authors.lastname: Siminovitch
authors.forename: Mario E
authors.initials: ME
authors.lastname: Beiner
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D009864:Ontario / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1