IIT Madras Study Uncovers Widespread Inherited Genetic Risk in Indian Breast Cancer Patients
A groundbreaking study conducted by the Indian Institute of Technology Madras (IIT-M) has revealed that one in every four Indian breast cancer patients carries inherited genetic variants that significantly elevate cancer risk. This research, which analyzed DNA from 479 breast cancer patients sourced from the National Cancer Tissue Biobank, found that these risk-raising variants extend far beyond the commonly tested BRCA1 and BRCA2 genes, which are known to boost lifetime risk up to 70%.
Key Findings on Genetic Variants and Testing Gaps
Using whole-exome sequencing, researchers examined the protein-coding parts of genes, analyzing 97 cancer-risk genes, including BRCA1, BRCA2, and 15 DNA-repair genes. The findings, published in the peer-reviewed medical journal BMC Cancer, showed that nearly 25% of patients had disease-causing (pathogenic) changes. However, only 8.35% of these were in BRCA genes, while at least 67% occurred in non-BRCA genes such as:
- TP53: A tumour suppressor gene
- MLH1: Involved in DNA mismatch repair
- NF1: Regulates cell growth
- RB1: Controls the cell cycle
Professor S Mahalingam, who heads the biobank at IIT-M, emphasized the implications: "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."
Breast Cancer Statistics and Recommendations for Improved Testing
Data from the state cancer registry indicates that in 2021, more women (43,163) were diagnosed with breast cancer compared to men (33,805). Among women aged 0-74, one in 11 had a cumulative risk of acquiring cancer, versus one in 12 men. Breast cancer accounts for at least 28% of cancers in women, followed by cervix (14%), ovary (6%), and corpus uteri (4%).
The study's authors, including contributors from Karkinos Healthcare, Kumaran Hospital, and Chennai Breast Centre, advocate for multi-gene panel tests or full exome sequencing to check dozens of genes simultaneously. They also stress the need for Indian-specific databases to identify variants more common in the local population. For instance, the research identified 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," noted Professor Mahalingam.
Additional Health Benefits and Chemotherapy Safety Insights
Beyond cancer risk, these genetic tests can flag other treatable health issues, such as Marfan syndrome, anaesthesia reactions, irregular heartbeats, or high cholesterol. John Peter, the study's first author from IIT-M's biotechnology department, explained: "These actionable alerts help prevent unrelated health problems, separate from the 25% cancer-risk variants studied."
The study also highlights the importance of checking chemotherapy safety genes before treatment. Co-author Bani Jolly from Karkinos Healthcare in Bengaluru pointed out: "We found DPYD flaws in 5% of patients, which can trigger severe side effects from common drugs like 5-FU used in cancer therapy. Routine tests before treatment are essential to reduce side effects and improve outcomes."
