There is substantial variability in cancer risk in women who have inherited a BRCA1 or BRCA2 (BRCA1/2) mutation. Numerous factors have been hypothesized to modify these risks, but studies are of variable quality, and it remains unclear which of these may be of value in clinical risk assessment.
Methods
PubMed and Web of Science databases were searched for articles published through September 2013. Fixed effects meta-analysis was done using the hazard ratios and/or odds ratios to estimate the pooled effect estimates (ES) and 95% confidence intervals (CIs) to identify factors that are associated with cancer risk modification in BRCA1/2 mutation carriers.
Results
We identified 44 nonoverlapping studies that met predefined quality criteria. Sufficient evidence is available to make clinically relevant inferences about a number of cancer risk modifiers. The only variable examined that produced a probable association was late age at first live birth, a meta-analysis showed a decrease in the risk of breast cancer in BRCA1 mutation carriers with women aged 30 years or older vs. women younger than 30 years (ES = 0.65; 95% CI =0.42 to 0.99). The same was shown for women aged 25 to 29 years versus those aged less than 25 years (ES = 0.69; 95% CI = 0.48 to 0.99). Breastfeeding and tubal ligation were associated with reduced ovarian cancer risk in BRCA1 mutation carriers; oral contraceptives were associated with reduced risk among BRCA1/2 mutation carriers. Smoking was associated with increased breast cancer risk in BRCA2 mutation carriers only.
Conclusions
Data assessing many potential risk modifiers are inadequate, and many have not been externally validated. Although additional studies are required to confirm some associations, sufficient information is available for some risk factors to be used in risk counseling or lifestyle modification to minimize cancer risk in BRCA1/2 mutation carriers
BRCA1 BRCA2 cancer risk modifiers, hereditary breast ovarian cancer risk factors, oral contraceptive BRCA mutation cancer, reproductive factors BRCA cancer modification, BRCA mutation carrier clinical risk assessment, systematic review meta-analysis BRCA, parity breastfeeding BRCA cancer risk, genetic cancer risk lifestyle modifiers, BRCA mutation penetrance variability
PMID 24824314 24824314 DOI 10.1093/jnci/dju091 10.1093/jnci/dju091
Cite this article
Friebel, T., Domchek, S., & Rebbeck, T. (2014). Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. Journal of the National Cancer Institute, 106(6), dju091. https://doi.org/10.1093/jnci/dju091
Friebel T, Domchek S, Rebbeck T. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju091. doi:10.1093/jnci/dju091
Friebel, Tara, et al. "Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis." Journal of the National Cancer Institute, vol. 106, no. 6, 2014, pp. dju091.
Keywords
BRCA1 Protein, BRCA1 Protein, Human, BRCA2 Protein, BRCA2 Protein, Human
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