title: MutYH mutation carriers have increased breast cancer risk.
abstract: BACKGROUND
  Variants of the mutY homolog gene MutYH, a DNA repair gene, are associated with increased risk of colorectal cancer; however, it remains unclear whether these variants also are associated with the risk of other cancers. The authors studied the risk of breast cancer associated with MutYH variants in a unique ethnic group of Sephardi Jews in Israel with a high prevalence of MutYH mutations.
  
  
  METHODS
  The study participants were 930 Sephardi Jewish women of North African origin who were recruited into the population-based case-control Breast Cancer in Northern Israel Study (BCINIS) either as breast cancer cases or as healthy controls. All participants contributed a blood sample and completed an interview. Two MutYH variants, a glycine-to-aspartic acid substitution at codon 396 (G396D) and a tyrosine-to-cysteine substitution at codon 179 (Y179C), were studied.
  
  
  RESULTS
  In the Sephardi Jews, among the healthy controls, 20 women (3.7%) were homozygote or heterozygote carriers of the G396D variant, and 4 women (0.7%) were heterozygote carriers of the Y179C variant. Breast cancer cases had a 6.7% prevalence of G396D, yielding a significantly elevated risk estimate for breast cancer (odds ratio, 1.86; 95% confidence interval, 1.02-3.39; P = .039). The tumors detected in carriers with MutYH variants were similar in characteristics to those without MutYH variants, as was the age at diagnosis.
  
  
  CONCLUSIONS
  Carriers of variants in MutYH, although not very common, may have an increased risk of breast cancer in Jews of North African origin. Identification of such carriers and special surveillance protocols may be warranted.
authors.affiliation: Department of Community Medicine and Epidemiology, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel. rennert@tx.technicon.ac.il
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Flavio
authors.initials: F
authors.lastname: Lejbkowicz
authors.forename: Ilana
authors.initials: I
authors.lastname: Cohen
authors.forename: Mila
authors.initials: M
authors.lastname: Pinchev
authors.forename: Hedy S
authors.initials: HS
authors.lastname: Rennert
authors.forename: Ofra
authors.initials: O
authors.lastname: Barnett-Griness
mesh_terms: D000352:Africa, Northern / Q000208:ethnology; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase