A groundbreaking study by researchers from the Indian Institute of Technology Madras (IIT Madras) and Karkinos Healthcare has revealed that almost 25% of Indian breast cancer patients carry inherited genetic variants linked to cancer risk, with the majority located outside the well-known BRCA1 and BRCA2 genes.
The research, among the largest germline genomics analyses conducted in India, was carried out in collaboration with Kumaran Hospital, Chennai, and the Chennai Breast Centre. Published in BMC Cancer, the study underscores the need to reevaluate current genetic testing strategies in India, which largely focus on BRCA genes or hotspot-based screening.
The study analyzed germline DNA from 479 unselected breast cancer patients collected through the National Cancer Tissue Biobank at IIT Madras and integrated into the Bharat Cancer Genome Atlas. Researchers found that 24.6% of patients carried pathogenic or likely pathogenic variants. Only 8.35% of these were associated with BRCA1/2 genes, while a larger share—11.9%—occurred in homologous recombination repair pathway genes. Overall, 67% of positive findings were in non-BRCA genes, including MLH1, NF1, TP53, and RB1.
These findings highlight the complexity of inherited breast cancer risk in India and point to the potential benefits of multi-gene panel or exome-based testing. The study also emphasizes the importance of developing India- and South Asia-specific genetic databases to improve risk assessment and prevent misclassification.
Beyond cancer predisposition, the research identified clinically significant secondary findings. Over 21% of patients carried actionable variants in non-cancer genes associated with cardiac disorders and metabolic diseases, and approximately 8% were carriers of recessive genetic conditions.
The study also stressed the relevance of pharmacogenomics in treatment planning. Variants in the DPYD gene, which can cause severe toxicity to commonly used chemotherapy drugs, were identified, supporting the case for routine genetic screening prior to therapy.
Researchers further uncovered ancestry-specific genetic variations, including India-enriched variants in BRCA1 and RECQL genes, which differ from global datasets. These findings reinforce the need for region-specific genomic research.
Experts believe the study’s results could significantly influence clinical practice, public health policy, and national cancer guidelines, advancing precision oncology and enabling more personalized treatment strategies tailored to India’s population.
