Chennai: Researchers from the Indian Institute of Technology Madras and Karkinos Healthcare have found that one in four Indian breast cancer patients carries an inherited cancer-linked genetic variant, most occurring beyond the commonly tested BRCA1 and BRCA2 genes.
The study analysed germline DNA from 479 patients using samples from the National Cancer Tissue Biobank at IIT Madras, making it one of the country’s largest hereditary breast cancer datasets.
Now part of the Bharat Cancer Genome Atlas, the findings call for expanded genetic testing strategies tailored to India’s population and support the development of precision oncology and improved risk-reduction approaches.
Elaborating on the key findings, Lead Author Prof. S. Mahalingam, Head, National Cancer Tissue Biobank, IIT Madras, said: “Our findings have direct implications for clinical practice, public health policy and national cancer guidelines. With approximately one in four Indian breast cancer patients carrying an inherited pathogenic variant—and most of these variants lying outside BRCA1/2—the study makes a compelling case for shifting from BRCA-only testing to broader multi-gene panel or exome-based germline testing in India. The data also reinforce the need for India- and South Asia–specific variant databases and interpretation frameworks to avoid misclassification and ensure accurate risk assessment in diverse populations.”
Dr John Peter, the first author of the study said: “Beyond cancer risk, the study uncovered important secondary health risks. More than 21 per cent of patients carried actionable variants in non-cancer genes associated with conditions such as Marfan syndrome, malignant hyperthermia susceptibility, inherited cardiac arrhythmias and familial hypercholesterolaemia. About 8 percent were carriers of recessive metabolic and genetic disorders, including biotinidase deficiency and Wilson disease. These findings demonstrate how comprehensive germline sequencing can uncover clinically meaningful information beyond cancer predisposition.”
Further, Dr Bani Jolly, said: “This study also highlights the importance of pharmacogenomics in chemotherapy safety. Clinically significant DPYD variants known to cause severe toxicity with fluoropyrimidine drugs such as 5-FU and capecitabine were observed at measurable frequency in this Indian cohort. The researchers detected the c.1679T>G (HapB3) variant in 3.13 per cent and the c.1905+1G>A variant in 1.67 per cent of patients, supporting strong consideration for routine DPYD genotyping prior to treatment initiation.”
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