title: Common MUTYH mutations and colorectal cancer risk in multiethnic populations.
abstract: MUTYH is associated with colorectal cancer (CRC) risk. We studied the frequency of MUTYH and risk of CRC in Arabs, North African and European Jews. Participants were all 593 Sephardi Moroccan Jews (232 cases, 361 controls) and all 631 Arabs (327 cases, 304 controls) recruited into a population-based study of colorectal cancer in Israel, as well as a random sample of 189 Ashkenazi Jewish cases. Two MUTYH mutations, G396D and Y179C, were studied in 1,413 individuals, with MUTYH sequence analysis in 46 cases with CRC in a sibling or adenoma. No carriers of mutations in MUTYH were identified in Ashkenazi Jews and only one in Arabs. In Sephardi Jews, 28 carriers of G396D, 25 (4.2%) heterozygotes and 3 (0.5%) homozygotes were identified. Four (0.7%) were heterozygote carriers of the Y179C mutation. Two compound heterozygous carriers of Y179C and G396D were identified. Homozygote carriers of G396D had nonsignificantly elevated risk of CRC (OR = 11.0, 95% CI: 0.91-213.9, p = 0.06), and combined bi-allelic carriers of G396D and Y179C had increased risk, OR = 17.4, 95% CI = (1.9-316.7, p = 0.009). Four of five bi-allelic carriers reported a family history of CRC. Sequencing of 46 colorectal cancer cases with family history and additional adenomas, did not identify any other non-founder mutations. MUTYH carriers of the two common founder mutations are profoundly under-represented among both Ashkenazi Jews and Arabs. The prevalence of MUTYH carriers of the common mutations is much higher in Sephardi Jews. Bi-allelic carriers of mutations in MUTYH, are associated with highly risk of colorectal cancer.
authors.affiliation: Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit Health Services National Cancer Control Center, Haifa, Israel.
authors.forename: Flavio
authors.initials: F
authors.lastname: Lejbkowicz
authors.forename: Ilana
authors.initials: I
authors.lastname: Cohen
authors.forename: Ofra
authors.initials: O
authors.lastname: Barnett-Griness
authors.forename: Mila
authors.initials: M
authors.lastname: Pinchev
authors.forename: Jen
authors.initials: J
authors.lastname: Poynter
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
mesh_terms: D000236:Adenoma / Q000208:ethnology / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D018912:Arabs / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase