Breast Cancer in Northwest Rajasthan Shows Distinct Genetic Signature, Study Finds

The findings were published in the International Journal of Health Sciences and Research by Sanjay Sharma, Assistant Professor, Department of Surgery, at Sardar Patel Medical College, and colleagues.

For the study, researchers performed genetic mapping on 32 modified radical mastectomy specimens to evaluate alterations in genes associated with breast cancer susceptibility. The analysis focused on P53, K-Ras, NAT2, KDMA6, and other relevant genetic markers.

The researchers found alterations in both P53 and K-Ras in all 32 samples. NAT2 gene amplification was detected in 15 cases (46.9%), while KDMA6 amplification was observed in only one case (3.1%).

Commenting on the findings, Dr. Sharma told Medical Dialogues that the study highlights the importance of understanding regional genetic differences in breast cancer. 

"The biggest takeaway is that breast cancer in this specific region has a unique genetic makeup that differentiates it from global data. We cannot simply rely on Western or global standards to treat local patients in Northwestern Rajasthan or other geographical regions of India," he said.

Dr. Sharma noted that the NAT2 finding is particularly significant because the gene is traditionally linked to bladder cancer rather than breast cancer. NAT2 plays a key role in detoxifying environmental carcinogens, including aromatic amines found in tobacco smoke, industrial pollutants, and heavily charred foods.

"Globally, NAT2 is known for its association with bladder cancer risk. However, our study found NAT2 gene amplification directly within breast tumors in 46.9% of patients," he said.

According to Dr. Sharma, gene amplification occurs when cancer cells create multiple copies of a gene, leading to excessive activity. The high prevalence of NAT2 amplification suggests a previously unrecognized role for the gene in breast cancer development within this population.

"Seeing NAT2 heavily duplicated inside breast tumors suggests that these cells may be responding to a unique burden of environmental or ingested toxins in our region. Since a large section of the population depends on agriculture, pesticide and fertilizer exposure may have contributed to alterations in body metabolism," he explained.

The study also revealed alterations in P53 and K-Ras in every sample analyzed. Dr. Sharma described this as an unusual finding compared with international reports, where P53 mutations occur in about 30% of breast cancers and K-Ras mutations in fewer than 5%.

"Finding alterations in both P53 and K-Ras in 100% of our samples points toward a distinct regional genetic profile," he said.

He explained that K-Ras acts as a growth-promoting gene, while P53 serves as a critical tumor-suppressor gene. When K-Ras is activated, and P53 loses its protective function, cells can undergo uncontrolled growth and accumulate genetic instability.

Dr. Sharma believes these findings could eventually support the development of regional genetic screening panels incorporating P53, K-Ras, and NAT2. Such markers may help identify high-risk individuals earlier, improve tumor characterization, and guide personalized treatment approaches. He also noted that NAT2 amplification could have implications for chemotherapy dosing because the gene is involved in drug metabolism.

The researchers plan to validate their findings through larger multi-center studies across Rajasthan and other parts of India, while also exploring possible links between environmental exposures and genetic alterations. Laboratory studies are also needed to determine whether targeting NAT2-related pathways could offer new therapeutic opportunities.

The authors concluded that, in addition to the established roles of P53 and K-Ras, NAT2 may represent a previously underrecognized contributor to breast cancer susceptibility in Northwest Rajasthan, warranting further investigation.