What question did this study set out to answer?

To determine whether specific types, functional impacts, and nucleotide positions of BRCA1 and BRCA2 mutations associate with differential risks of breast versus ovarian cancer.

April 7, 2015JAMAOpen Access

Association of Type and Location ofBRCA1andBRCA2Mutations With Risk of Breast and Ovarian Cancer

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To determine whether specific types, functional impacts, and nucleotide positions of BRCA1 and BRCA2 mutations associate with differential risks of breast versus ovarian cancer.
Conducted an international observational study of 19,581 female BRCA1 carriers and 11,900 female BRCA2 carriers recruited across 55 centers in 33 countries between 1937 and 2011 (median, 1999).
Calculated hazard ratios for breast and ovarian cancer by mutation type, function (including nonsense-mediated decay), and nucleotide position, alongside the relative hazard ratio (RHR) comparing breast versus ovarian cancer risk.
In BRCA1 carriers, 46% developed breast cancer and 12% ovarian cancer, with 3 breast cancer cluster regions identified (c.179 to c.505 [RHR=1.46; 95% CI, 1.22-1.74; P=2×10⁻⁶]; c.4328 to c.4945 [RHR=1.34; 95% CI, 1.01-1.78; P=.04]; c.5261 to c.5563 [RHR=1.38; 95% CI, 1.22-1.55; P=6×10⁻⁹]) and 1 ovarian cluster region (c.1380 to c.4062 [RHR=0.62; 95% CI, 0.56-0.70; P=9×10⁻¹⁷]).
In BRCA2 carriers, 52% developed breast cancer and 6% ovarian cancer, with multiple breast cancer cluster regions identified (c.1 to c.596 [RHR=1.71; 95% CI, 1.06-2.78; P=.03]; c.772 to c.1806 [RHR=1.63; 95% CI, 1.10-2.40; P=.01]; c.7394 to c.8904 [RHR=2.31; 95% CI, 1.69-3.16; P=.00002]) and 2 ovarian cluster regions (c.3249 to c.5681 [RHR=0.51; 95% CI, 0.44-0.60; P=6×10⁻¹⁷]; c.6645 to c.7471 [RHR=0.57; 95% CI, 0.41-0.80; P=.001]).
Mutations causing nonsense-mediated decay were linked to significant differences in cancer risk distribution and an earlier age of breast cancer onset across carriers of both genes.

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Implication

Observational study reveals breast and ovarian cancer risks vary by mutation type and position in BRCA1 and BRCA2 carriers, suggesting potential value for tailored cancer risk assessment.

Cite This Study

Rebbeck et al. (2015) studied this question.

synapsesocial.com/papers/6a93f82c00963b0dd7fc0d5b https://doi.org/10.1001/jama.2014.5985

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Implication

Observational study reveals breast and ovarian cancer risks vary by mutation type and position in BRCA1 and BRCA2 carriers, suggesting potential value for tailored cancer risk assessment.

Association of Type and Location ofBRCA1andBRCA2Mutations With Risk of Breast and Ovarian Cancer

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Discussion

Implication

Cite This Study

Association of Type and Location ofBRCA1andBRCA2Mutations With Risk of Breast and Ovarian Cancer

Key Points

Discussion

Implication

Cite This Study

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