Abstract
Advances in gene sequencing of mutations related to hereditary cancers have enabled expansion of this testing to patients cared for in community clinics. Our goal was to report on the prevalence of pathogenic/likely pathogenic variants (PV/LPV) and the distribution of mutations by cancer history in a diverse cohort. We evaluated 3162 women in a large non-profit health plan who were referred for cancer genetic counseling and tested them via the same multigene cancer panel. We examined the pathogenic variant/likely pathogenic variant (PV/LPV) prevalence for 20 genes by clinical factors, demographics, and personal or family cancer history. We calculated adjusted odds ratios for the association between race/ethnicity and mutation results. The majority of women (65.4%) were referred post-breast or ovarian cancer diagnosis. The overall prevalence of any PV/LPV result was 11.7%. Overall, nearly 5.4% had BRCA1/2 mutations, while 6.3% had at least one mutation in non-BRCA genes. In the subset with any PV/LPV result, 55.0% of the total mutations were in non-BRCA genes. The distribution of mutations was similar in those with or without a personal cancer history. Latina women were somewhat less likely to have mutations in non-BRCA genes implicated with breast cancer (OR = 0.55, 95% CI 0.36–0.87). Given that 55.0% of the PV/LPV results were in genes other than BRCA1/2, regardless personal or family cancer history, the study suggests that multigene cancer panel testing may be appropriate for detecting germline mutations in a high-risk cohort in a managed care or public health setting.
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Acknowledgments
The authors thank Xiaoqing Xu for assistance with programming.
Funding
This study was funded by Kaiser Permanente Southern California, Department of Research & Evaluation.
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Kaiser Permanente Southern California (KPSC) received a grant from GeneDx to support conference travel for Mónica Alvarado, MS LCGC and Reina Haque, PhD.
George E. Tiller, MD PhD and Joanie Chung, MPH declare no conflict of interest.
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The study was reviewed and approved by the KPSC Internal Review Board. All procedures followed the standards of the KPSC IRB and with the 1975 Helsinki Declaration, and its later amendments or comparable ethical standards. The KPSC IRB waived informed written consent for this observational data-only study.
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Alvarado, M., Tiller, G.E., Chung, J. et al. Prevalence of mutations in a diverse cohort of 3162 women tested via the same multigene cancer panel in a managed care health plan. J Community Genet 11, 359–366 (2020). https://doi.org/10.1007/s12687-020-00456-6
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DOI: https://doi.org/10.1007/s12687-020-00456-6