Indian Institute of Technology Madras study reveals need for broader breast cancer testing in India as commonly tested BRCA1 and BRCA2 genes account for less than 8% of cases

Chennai: One in four Indian breast cancer patients carries inherited genetic variants that raise cancer risk beyond the commonly tested BRCA1 and BRCA2 genes — which can boost lifetime risk up to 70% — found a study by Indian Institute of Technology Madras.

Researchers at IIT-M examined DNA from 479 breast cancer patients sourced from the National Cancer Tissue Biobank. They sequenced the protein-coding parts of these genes using whole-exome sequencing and analysed 97 cancer-risk genes, including BRCA1, BRCA2, and 15 DNA-repair genes, classifying variants according to global standards. Findings published in the peer-reviewed medical journal BMC Cancer showed that while nearly 25% of patients had disease-causing (pathogenic) changes, only 8.35% carried BRCA genes. At least 67% occurred in non-BRCA genes such as TP53 (a tumour suppressor), MLH1 (DNA mismatch repair), NF1 (cell growth regulator), and RB1 (cell cycle controller). "This means two-thirds of risk-raising variants hide outside the famous BRCA1/BRCA2. But genetic testing in India focuses on these two genes or specific hotspots. So, we miss most risks," said Professor S Mahalingam, who heads the biobank at IIT-M.


Data from the state cancer registry shows that in 2021 — the latest available data — more women (43,163) were diagnosed with the disease compared to men (33,805). One in 11 women in the 0-74 age group had a cumulative risk of acquiring cancer compared to one in 12 men. At least 28% of cancers in women are breast cancers, followed by cervix (14%), ovary (6%), and corpus uteri (4%).

Authors of the study, including those from Karkinos Healthcare and Chennai-based Kumaran Hospital and Chennai Breast Centre recommend multi-gene panel tests — checking dozens of genes at once — or full exome sequencing, and Indian-specific databases for variants more common here. For instance, the study found a potential new RECQL gene change linked to breast cancer risk. "We must do larger studies to establish a longer list of high-risk genes, but we know that testing for just BRCA is insufficient," he said.

Additionally, these genetic tests flag treatable problems such as Marfan syndrome, anaesthesia reactions, irregular heartbeats, or high cholesterol. "These actionable alerts help prevent unrelated health problems, separate from the 25% cancer-risk variants studied," said the study's first author, John Peter, who works with IIT-M's biotechnology department.

The study stresses checking chemo safety genes beforehand, said a co-author Bani Jolly from Bengaluru-based Karkinos Healthcare. "We found DPYD flaws in 5% of patients, which can trigger severe side effects from common drugs such as 5-FU used in cancer therapy. Routine tests before treatment are essential to reduce side effects and improve outcomes," Jolly said.