{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T04:49:28Z","timestamp":1692766168844},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T00:00:00Z","timestamp":1654905600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To investigate the role of interaction of tobacco metabolizing polymorphic cytochrome P450s (CYPs) and glutathione S\u2010transferase M1 (GSTM1) with environmental risk factors in modifying the susceptibility to head and neck squamous cell carcinoma (HNSCC), a case\u2013control study with 1250 proven cases of HNSCC and equal number of healthy controls was planned. A small but significant increase in the risk to HNSCC (1\u20132 fold) in the cases with variant genotypes of <jats:italic>CYPs<\/jats:italic> (<jats:italic>1A1<\/jats:italic> or <jats:italic>1B1<\/jats:italic> or <jats:italic>2E1)<\/jats:italic> increased several folds (up to 13 fold) in regular tobacco or alcohol users. This several fold increase in risk could be due to more than multiplicative interaction observed between the risk genotypes of <jats:italic>CYPs<\/jats:italic> and tobacco or alcohol. A synergistic effect was also observed between tobacco as well as alcohol users among cases with risk genotypes of <jats:italic>CYPs<\/jats:italic> and <jats:italic>GSTM1<\/jats:italic> that resulted in a further increase in risk (up to 29 fold) to HNSCC. Interestingly, the increase in the risk in tobacco users among cases with variant genotypes of <jats:italic>CYPs<\/jats:italic> or a combination of <jats:italic>CYPs<\/jats:italic> &amp; <jats:italic>GSTM1 (\u2212)<\/jats:italic> was associated with a higher mRNA expression of <jats:italic>CYPs<\/jats:italic> when compared to nontobacco users in controls with wild type of genotypes of <jats:italic>CYPs<\/jats:italic> &amp; <jats:italic>GSTM1<\/jats:italic>. The data suggest that the interaction of genetic and environmental risk factors leads to increased expression of <jats:italic>CYPs<\/jats:italic> which may increase the levels of tobacco\u2010derived carcinogens thereby modifying the risk to HNSCC.<\/jats:p>","DOI":"10.1002\/em.22495","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T11:09:55Z","timestamp":1653995395000},"page":"255-264","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interaction of cytochrome P450s with environmental risk factors increases their expression and risk to head and neck cancer"],"prefix":"10.1002","volume":"63","author":[{"given":"Tridiv","family":"Katiyar","sequence":"first","affiliation":[{"name":"System Toxicology and Health Risk Assessment Group CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR), Vishvigyan Bhawan, Mahatma Gandhi Marg  Lucknow India"},{"name":"Department of Biochemistry Babu Banarsi Das University  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinay","family":"Yadav","sequence":"additional","affiliation":[{"name":"System Toxicology and Health Risk Assessment Group CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR), Vishvigyan Bhawan, Mahatma Gandhi Marg  Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feza","family":"Hasan","sequence":"additional","affiliation":[{"name":"System Toxicology and Health Risk Assessment Group CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR), Vishvigyan Bhawan, Mahatma Gandhi Marg  Lucknow India"},{"name":"Department of Biochemistry Babu Banarsi Das University  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arvind P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Life Sciences Central University of Rajasthan  Ajmer India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Biochemistry All India Institute of Medical Sciences (AIIMS)  Raebareli India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy King George's Medical University  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahat","family":"Hadi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Dr. Ram Manohar Lohia Institute of Medical Sciences  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madan Lal B.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy King George's Medical University  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devendra","family":"Parmar","sequence":"additional","affiliation":[{"name":"System Toxicology and Health Risk Assessment Group CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR), Vishvigyan Bhawan, Mahatma Gandhi Marg  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,11]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","first-page":"e116421\u20109","article-title":"Prevalence and determinants of co\u2010use of alcohol and tobacco among men in working age group (18\u201059\u2009years) in India","volume":"13","author":"Anand A.","year":"2016","journal-title":"Epidemiology, Biostatistics, and Public Health"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1996.0153"},{"issue":"2","key":"e_1_2_8_4_1","first-page":"174","article-title":"Genetic and Environmental Factors in Head and Neck Cancer Genesis","volume":"26","author":"Baez A.","year":"2008","journal-title":"Journal of Environmental Science and Health. 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