Genetic testing for hereditary breast and ovarian cancer in Indian population: A single institutional study.

Abstract

e13153 Background: Women with Hereditary breast ovarian cancer have an increased lifetime risk of developing breast, ovarian and other second primary cancers . A number of genes including BRCA 1 & 2 have been implicated in Hereditary Breast Ovarian Cancer. In this background we sought to analyze the genetic pattern of patients who underwent genetic testing as per the NCCN criteria for hereditary breast ovarian cancer syndrome. Methods: All consecutive patients who fit into the NCCN criteria for genetic testing for Hereditary Breast Ovarian Cancer from 2016 to 2018 were referred to our genetic clinic. The data of all the patients who underwent further genetic testing after counselling were collected and analyzed. Results: Out of 155 patients who underwent genetic testing ,131 patients were found eligible for the study.127 were female and 4 were male. There were 27 pathogenic mutations identified while 32 were variants of unknown significance . The remaining 72 were negative for any of the known mutations. 22 were pathogenic for BRCA 1 Mutation , two pathogenic for BRCA 2 and one for TP53 ,PALB2 and ATM each. Out of the 32 VUS, 9 were BRCA 2, 4 in CDH 1, 2 in BRCA1, CHEK2 ,MSH2 and BRIP1 and one each in MLH1, MLH3, ATM, APC, RAD51D, XRCC3, NBN, TP53.Three patients had double VUS reported. BRCA 1 is the most common pathogenic mutation ( 16.79% ) found while BRCA 2 is the most common VUS reported ( 28 %). Conclusions: 20.6 % of eligible patients had pathogenic mutations which is much higher than the western literature. However the VUS rates in Indian population are high 22% owing to a paucity of genetic data of Indian population. Multigene testing helps in identifying other genes asscociated with the Hereditary breast ovarian cancer criteria in addition to BRCA 1 & 2.