Journal of the National Cancer Institute · 2004
BRCA1 and BRCA2 founder mutations and the risk of colorectal cancer.
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Niell Bethany L, Rennert Gad, Bonner Joseph D, Almog Ronit, Tomsho Lynn P, Gruber Stephen B
Аннотация
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.
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.
Предметные рубрики MeSH
AgedBreast NeoplasmsCase-Control StudiesColorectal NeoplasmsDNA Mutational AnalysisFemaleFounder EffectGenes, BRCA1Genes, BRCA2Genetic Predisposition to DiseaseGenotypeHeterozygoteHumansIsraelJewsMaleMatched-Pair AnalysisMiddle AgedMultivariate AnalysisMutationOdds RatioResearch DesignRisk AssessmentRisk Factors