Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations

Breast Cancer Res Treat. 2018 Jul;170(1):189-196. doi: 10.1007/s10549-018-4726-x. Epub 2018 Feb 22.

Abstract

Purpose: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized.

Methods: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform.

Results: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2.

Conclusion: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.

Keywords: BRCA1; BRCA2; Breast cancer; Multi-gene panel; Next-generation sequencing.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast / pathology
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Early Detection of Cancer
  • Fanconi Anemia Complementation Group N Protein / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • India / epidemiology
  • Mass Screening
  • Middle Aged
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53