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An increase in the risk of HNSCC and its subsites (larynx, pharynx, and oral cavity) was observed among the cases with null genotypes of GSTM1 (odds ratio [OR] = 1.87) or GSTT1 (OR = 1.39) while reduced risk (OR = 0.81) was observed the cases with variant genotype of GSTP1. Tobacco use in the form of smoking or chewing interacted multiplicatively with GSTM1 or GSTT1 to increase the risk several folds (3\u201310 folds) in HNSCC and its subsites. Alcohol use also increased the risk (2\u20133 folds) to HNSCC and its subsites in cases with null or variant genotypes of GSTs, though this risk was of lesser magnitude when compared to the tobacco users. A synergistic effect of both, tobacco smoking and alcohol drinking, led to several folds (25\u2010folds) increased risk to HNSCC among the cases with null genotype of GSTM1 and GSTT1 when compared to nonsmokers and nondrinkers with wild genotype of GSTM1 and GSTT1 in controls. Furthermore, cases with variant genotypes of GSTP1 (Val\/Val) showed superior treatment response with improved survival rate and lower risk of death when compared to the patients with wild type genotype (Ile\/Ile). The data suggest that though polymorphism in GSTs may be a modest risk factor for determining HNSCC risk, gene\u2010environment interactions significantly modify the susceptibility to HNSCC by several folds.<\/jats:p>","DOI":"10.1002\/em.22362","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T06:05:32Z","timestamp":1582005932000},"page":"574-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Interaction of glutathione\u2010s\u2010transferase genotypes with environmental risk factors in determining susceptibility to head and neck cancer and treatment response and survival outcome"],"prefix":"10.1002","volume":"61","author":[{"given":"Tridiv","family":"Katiyar","sequence":"first","affiliation":[{"name":"System Toxicology &amp; Health Risk Assessment Group CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR)  Lucknow Uttar Pradesh India"},{"name":"Babu Banarsi Das University  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Yadav","sequence":"additional","affiliation":[{"name":"System Toxicology &amp; Health Risk Assessment Group CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR)  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailendra S.","family":"Maurya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology\u2010Oncology, Developmental Biology and Genetics Washington University  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munindra","family":"Ruwali","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology Amity University  Gurgaon Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu","family":"Singh","sequence":"additional","affiliation":[{"name":"Balrampur Hospital  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feza","family":"Hasan","sequence":"additional","affiliation":[{"name":"System Toxicology &amp; Health Risk Assessment Group CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR)  Lucknow Uttar Pradesh India"},{"name":"Babu Banarsi Das University  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery and Department of Radiotherapy King George's Medical University  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery and Department of Radiotherapy King George's Medical University  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery and Department of Radiotherapy King George's Medical University  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shambhavi","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Statistics University of Lucknow  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahat","family":"Hadi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Dr. Ram Manohar Lohia Institute of Medical Sciences  Lucknow Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madan L. 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