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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\u2013control study of 190 gastric cancer patients recruited at the hospitals and 317 healthy community controls, integrating PCR-based genotyping of\n                    <jats:italic>GSTM1<\/jats:italic>\n                    ,\n                    <jats:italic>GSTT1<\/jats:italic>\n                    ,\n                    <jats:italic>CYP2E1<\/jats:italic>\n                    ,\n                    <jats:italic>TLR2<\/jats:italic>\n                    ,\n                    <jats:italic>TLR4<\/jats:italic>\n                    ,\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>IL-10<\/jats:italic>\n                    with detailed assessment of lifestyle, diet, and\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    infection, alongside ARMS\n                    <jats:sup>\u00ae<\/jats:sup>\n                    -based qBiomarker\u2122 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\u20133.43;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Among ever tobacco chewers, individuals carrying the\n                    <jats:italic>GSTM1<\/jats:italic>\n                    -null genotype had a markedly higher risk than tobacco chewers carrying the\n                    <jats:italic>GSTM1<\/jats:italic>\n                    non-null genotype (adjusted OR 12.63, 95% CI 3.04\u201352.42;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Regular consumption of pumpkin, tomatoes, cabbage, and seasonal fruits reduced gastric cancer risk by 40\u201370%. Germline mutations were frequent in\n                    <jats:italic>TP53<\/jats:italic>\n                    (81.25%),\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    (71.25%),\n                    <jats:italic>APC<\/jats:italic>\n                    (53.75%), and\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    (31.25%), suggesting possible inherited susceptibility and founder mutations in these populations. This study highlights strong gene\u2013environment 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\u2019s unique populations.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-50133-w","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T13:37:26Z","timestamp":1778074646000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic susceptibility and gene\u2013environment interactions in gastric cancer among ethnic populations of Northeast India"],"prefix":"10.1038","volume":"16","author":[{"given":"Kangjam Rekha","family":"Devi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debdutta","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjib","family":"Phukan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandakini","family":"Gogoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Majumdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Khamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwar","family":"Narain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"50133_CR1","first-page":"34","volume":"34","author":"K Singh","year":"2025","unstructured":"Singh, K., Grover, A. & Dhanasekaran, K. 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