Genetic susceptibility and gene-environment interactions in gastric cancer among ethnic populations of Northeast India.

Northeast India has a high burden of gastric cancer, but the factors driving this elevated risk remain poorly understood. This study examined genetic polymorphisms, germline mutations, and lifestyle factors contributing to gastric cancer risk in populations from Nagaland and Tripura. We conducted a case-control study of 190 gastric cancer patients recruited at the hospitals and 317 healthy community controls, integrating PCR-based genotyping of GSTM1, GSTT1, CYP2E1, TLR2, TLR4, TNF-α, and IL-10 with detailed assessment of lifestyle, diet, and Helicobacter pylori infection, alongside ARMS®-based qBiomarker™ mutation arrays for sensitive detection of germline cancer-associated variants. The GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (adjusted OR 2.26, 95% CI 1.49-3.43; p < 0.001). Among ever tobacco chewers, individuals carrying the GSTM1-null genotype had a markedly higher risk than tobacco chewers carrying the GSTM1 non-null genotype (adjusted OR 12.63, 95% CI 3.04-52.42; p < 0.001). Regular consumption of pumpkin, tomatoes, cabbage, and seasonal fruits reduced gastric cancer risk by 40-70%. Germline mutations were frequent in TP53 (81.25%), CTNNB1 (71.25%), APC (53.75%), and CDKN2A (31.25%), suggesting possible inherited susceptibility and founder mutations in these populations. This study highlights strong gene-environment interactions, frequent germline mutations, and the protective role of diet in gastric cancer risk. The findings emphasize the need for population-specific genetic screening, counselling, and preventive strategies tailored to Northeast India's unique populations.