Anticipating the arrival of low-penetrance genetic testing to primary care medicine
- 87 Downloads
Primary prevention is a pillar of primary care medicine. Furthermore, the identification of commonly occurring genetic mutations that confer only modest increases in disease risk (i.e., low-penetrance mutations or LPMs) is expanding our conception of how genetic testing supports prevention goals. To date, most predictive genetic testing has focused on identifying the minority of patients who carry mutations that significantly increase their risk for developing future disease (i.e., high-penetrance mutations or HPMs). Genetic tests for LPMs are more similar in structure and purpose to commonly used biomarker tests like lipid testing than to HPM testing. In the primary care setting, LPM testing will likely be presented to patients as one part of a multifactorial risk assessment that contains only a small amount of genetics-specific information. Consequently, preparing primary care clinicians for the anticipated use of LPM genetic tests will not require development of a completely new skill set but rather a re-conceptualization of both genetic testing and biomarker evaluation for primary prevention.
Dr. Tarini was supported by a K23 Mentored Patient-Oriented Research Career Development Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K23HD057994). Dr. Zikmund-Fisher was supported by a Mentored Research Scholar Grant from the American Cancer Society (MRSG-06-130-01-CPPB). Ms. Exe was supported by a genomics center supplemental award to the Ann Arbor VA Health Services Research & Development Center of Excellence. The funding agreements ensured the authors’ independence in designing the studies, interpreting the data, and publishing the report.
Conflict of interest
The authors declare that there are no conflicts of interest.
- Expert Panel on Detection, E., and Treatment of High Blood Cholesterol in Adults (2001) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, pp. 2486–2497Google Scholar
- King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, Tait J, Ford L, Dunn BK, Costantino J, Wickerham L, Wolmark N, Fisher B (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286:2251–2256PubMedCrossRefGoogle Scholar
- Kury S, Buecher B, Robiou-du-Pont S, Scoul C, Colman H, Le Neel T, Le Houerou C, Faroux R, Ollivry J, Lafraise B, Chupin LD, Sebille V, Bezieau S (2008) Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study. BMC Cancer 8:326PubMedCrossRefGoogle Scholar
- Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, Aulchenko Y, Lumley T, Kottgen A, Vasan RS, Rivadeneira F, Eiriksdottir G, Guo X, Arking DE, Mitchell GF, Mattace-Raso FU, Smith AV, Taylor K, Scharpf RB, Hwang SJ, Sijbrands EJ, Bis J, Harris TB, Ganesh SK, O’Donnell CJ, Hofman A, Rotter JI, Coresh J, Benjamin EJ, Uitterlinden AG, Heiss G, Fox CS, Witteman JC, Boerwinkle E, Wang TJ, Gudnason V, Larson MG, Chakravarti A, Psaty BM, van Duijn CM (2009) Genome-wide association study of blood pressure and hypertension. Nat Genet 41(6):677–687PubMedCrossRefGoogle Scholar
- Rebbeck TR, Friebel T, Lynch HT, Neuhausen SL, van ’t Veer L, Garber JE, Evans GR, Narod SA, Isaacs C, Matloff E, Daly MB, Olopade OI, Weber BL (2004) Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 22:1055–1062PubMedCrossRefGoogle Scholar