title: BRCA1 and BRCA2 founder mutations and the risk of colorectal cancer.
abstract: BACKGROUND
  Mutations in BRCA1 and/or BRCA2 (BRCA1/2) profoundly increase the risks of breast and ovarian cancers, but it is unclear whether mutations in these genes increase the risk of colorectal cancer. We investigated BRCA1/2 founder mutations and a family history of breast cancer as potential risk factors for colorectal cancer.
  
  
  METHODS
  In the population-based Molecular Epidemiology of Colorectal Cancer study in northern Israel, 1422 case patients with incident colorectal cancer, diagnosed between March 31, 1998, and December 31, 2002, and 1566 control subjects without colorectal cancer were genotyped for the BRCA1 187delAG, BRCA1 5385insC, and BRCA2 6174delT founder mutations. Genotypes and interview data from all case patients and control subjects and from only those of Ashkenazi Jewish descent (1002 case patients and 1038 control subjects) were used to calculate odds ratios [ORs] from logistic regression.
  
  
  RESULTS
  Twenty-four (2.4%) case patients and 20 (1.9%) control subjects carried one of the three mutations (OR = 1.24, 95% confidence interval [CI] = 0.68 to 2.26). A family history of breast cancer in a female relative was not associated with an increased risk of colorectal cancer, even after adjustment for the presence of a BRCA founder mutation (OR = 1.03, 95% CI = 0.75 to 1.41).
  
  
  CONCLUSIONS
  Although weak associations cannot be excluded, Ashkenazi BRCA founder mutations do not confer a strongly elevated risk of colorectal cancer. Similarly, a family history of breast cancer does not appear to be a strong risk factor for colorectal cancer in this population.
authors.affiliation: Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, MI 48109-0638, USA.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Niell
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bonner
authors.forename: Ronit
authors.initials: R
authors.lastname: Almog
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Tomsho
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000208:ethnology / Q000235:genetics*; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors