A major genomic study conducted by researchers from the Indian Institute of Technology Madras (IIT Madras) and Karkinos Healthcare has revealed that nearly one in four breast cancer patients in India carry inherited genetic risk variants linked to cancer, and importantly, most of these variants are found outside the well-known BRCA1 and BRCA2 genes. These findings, published in the peer-reviewed journal BMC Cancer, provide new insights into the genetic landscape of breast cancer in India and have significant implications for testing, treatment, and public-health policy.
Researchers analysed germline DNA from 479 unselected Indian breast cancer patients, with samples coming from the National Cancer Tissue Biobank at IIT Madras. This makes it one of the largest population-based hereditary breast cancer datasets studied in the country. The data have now also become part of the Bharat Cancer Genome Atlas, a large open-access genome resource for cancer research in India.
Here are the key findings of the study:
Genetic Risk Beyond BRCA Genes
About 24.6 % of the patients carried at least one pathogenic or likely pathogenic inherited variant associated with cancer risk.
Only around 8.35 % had inherited variants in the BRCA1 or BRCA2 genes, which are the genes most commonly tested in clinical practice worldwide.
A larger share — 11.9 % — had inherited mutations in other genes involved in DNA repair pathways, such as homologous recombination repair.
Overall, about 67 % of all positive findings were in non-BRCA genes, including MLH1, NF1, TP53 and RB1 — genes known to influence cancer susceptibility.
Implications for Genetic Testing
The researchers argue that the current focus on testing only BRCA1 and BRCA2 — a common practice in many clinical settings — is not sufficient for the Indian population. Since a majority of inherited risk variants lie outside these two genes, cancer genetic testing strategies in India should move towards broader multi-gene panels or even whole-exome germline testing tailored to regional genetic diversity.
Clinical and Public-Health Significance
The study’s lead author, Prof. S. Mahalingam, head of the National Cancer Tissue Biobank at IIT Madras, highlighted that these findings have direct implications for clinical care and national health policy.
Broader germline testing could improve risk assessment, help identify high-risk individuals earlier, and guide more personalised treatment plans.
The data also support building India- and South Asia-specific genetic variant databases so that risk assessments are accurate and relevant for local populations, avoiding misclassification based on data from other regions.
Additional Findings
The researchers found that more than 21 % of patients carried actionable variants in genes not directly linked to cancer but associated with other inherited conditions — such as familial hypercholesterolaemia, inherited cardiac arrythmias, and risks related to drug metabolism. About 8 % of patients were carriers of recessive disease variants that could have implications for their families.
Overall, this study challenges the traditional BRCA-centric approach and underscores the genetic complexity of breast cancer risk in the Indian population. It points to the importance of expanded genetic testing in clinical practice and the need for population-specific data to enhance early detection, risk reduction, and personalised care.