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Comparative Study
. 2001 Feb;68(2):410-9.
doi: 10.1086/318181. Epub 2001 Jan 19.

Variation in cancer risks, by mutation position, in BRCA2 mutation carriers

D Thompson  1 , D Easton; Breast Cancer Linkage Consortium
Affiliations
Comparative Study

Variation in cancer risks, by mutation position, in BRCA2 mutation carriers

D Thompson et al. Am J Hum Genet. 2001 Feb.

Abstract

Cancer occurrence in 164 families with breast/ovarian cancer and germline BRCA2 mutations was studied to evaluate the evidence for genotype-phenotype correlations. Mutations in a central portion of the gene (the "ovarian cancer cluster region" [OCCR]) were associated with a significantly higher ratio of cases of ovarian:breast cancer in female carriers than were mutations 5' or 3' of this region (P<.0001), extending previous observations. The optimal definition of the OCCR, as judged on the basis of deviance statistics, was bounded by nucleotides 3059-4075 and 6503-6629. The relative and absolute risks of breast and ovarian cancer associated with OCCR and non-OCCR mutations were estimated by a conditional likelihood approach, conditioning on the set of mutations observed in the families. OCCR mutations were associated both with a highly significantly lower risk of breast cancer (relative risk [RR] 0.63; 95% confidence interval (95% CI) 0.46-0.84; P=.0012) and with a significantly higher risk of ovarian cancer (RR = 1.88; 95% CI = 1.08-3.33; P=.026). No other differences in breast or ovarian cancer risk, by mutation position, were apparent. There was some evidence for a lower risk of prostate cancer in carriers of an OCCR mutation (RR = 0.52; 95% CI = 0.24-1.00; P=.05), but there was no evidence of a difference in breast cancer risk in males. By age 80 years, the cumulative risk of breast cancer in male carriers of a BRCA2 mutation was estimated as 6.92% (95% CI = 1.20%-38.57%). Possible mechanisms for the variation in cancer risk are suggested by the coincidence of the OCCR with the RAD51-binding domain.

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Figures

Figure 1
Figure 1
Counts of breast cancer and ovarian cancer, by mutation location within BRCA2. Counts exclude tested noncarriers and other known sporadic cases.
Figure 2
Figure 2
Cumulative incidence, in BRCA2-mutation carriers, of breast cancer (A) and ovarian cancer (B), by mutation location
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIN), http://www.ncbi.nlm.nih.gov/Omim (for inherited breast cancer type 2 [MIM 600185])

References

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