Table 1 Common diseases in which a positive genetic test result is associated with changes to clinical management options for the patient
From: Addressing the routine failure to clinically identify monogenic cases of common disease
Common disease | Genes | Prevalence of “Disease Associated Variants” in general population | Prevalence of “Disease Associated Variants” in specific common disease | Potential targeted interventions associated with monogenic attribution | Guidelines related to diagnosis and/or management of the common disease and its monogenic forms | ||
|---|---|---|---|---|---|---|---|
Pharmacologic therapy | Non-pharmacologic interventions | Professional organization(s) | Reflexive genetic testing recommended following diagnosis | ||||
Ovarian cancersa | BRCA1 BRCA2 | 1:200 [5] | Poly ADP ribose polymerase (PARP) inhibitors [13] | Bilateral mastectomy [14] | National Comprehensive Cancer Network (NCCN) [15] American Society of Clinical Oncology (ASCO) [16] | Yes | |
Breast cancer | BRCA1 BRCA2 | 1:200 [5] | PARP inhibitors [13] | Contralateral mastectomy Bilateral oophorectomy [19] | American Society of Breast Surgeons [20]b | Yes | |
Pancreatic cancer | BRCA1 BRCA2 | 1:200 [5] | 1:10 [21] | PARP inhibitors [22] | -- | NCCN [15] | Yes |
Colorectal cancer | MLH1 MSH2 MSH6 PMS2 | 1:280 [23] | 1:25 to 1:50 [24] | First-line therapy with pembrolizumab in advanced disease [25] | Transvaginal ultrasound, endometrial biopsy, hysterectomy [26] | Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group [27] | Yesc |
Coronary artery disease | LDLR APOB PCSK9 | 1:250 [3] | Lipid lowering for secondary prevention [combine statins with other lipid-lowering therapies as needed] | -- | 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol [30] | Not addressed | |
Hypertrophic cardiomyopathy | MYH7 MYBPC3 TNNI3 TNNT2 TPM1 MYL2 MYL3 ACTC1 HCM Mimics: [31] PRKAG2 LAMP2 GAA GLA TTR | If HCM mimic identified: enzyme replacement therapy (GAA, GLA) Antiarrhythmic drugs, ablation (PRKAG2) Transthyretin stabilizing or silencing drugs (TTR) | If HCM mimic identified: ICD implantation (LAMP2) | American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [35] | Yes | ||