{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:06:45Z","timestamp":1764781605237},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,6,7]],"date-time":"2004-06-07T00:00:00Z","timestamp":1086566400000},"content-version":"vor","delay-in-days":158,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polymorphisms in DNA\u2010repair genes could contribute to the interindividual differences in cancer susceptibility in smokers. By reducing DNA\u2010repair capacity, these polymorphisms may influence the net level of smoking\u2010induced genetic damage significantly, a critical step in the cascade of events leading to cancer. In this biomonitoring study, we examined the relationship between polymorphisms in the DNA\u2010repair gene <jats:italic>XPD\/ERCC2<\/jats:italic> and genetic damage. We tested the hypothesis that coding polymorphisms in <jats:italic>XPD\/ERCC2<\/jats:italic> limit DNA\u2010repair efficiency in humans leading to increased frequencies of chromosome aberration (CA) in their lymphocytes. We also used the mutagen\u2010sensitivity assay, with the tobacco\u2010specific nitrosamine NNK as a model mutagen, to determine whether lymphocytes from individuals with the variant <jats:italic>XPD<\/jats:italic> alleles are more sensitive to this tobacco\u2010specific carcinogen. We calculated odds ratios (ORs) as estimates of relative risk of increased frequencies of CA associated with two <jats:italic>XPD<\/jats:italic> polymorphisms (Asp312Asn in exon 10 and Lys751Gln in exon 23). We observed a 2.57\u2010fold (95% confidence limit [CL] = 0.88\u20137.50; <jats:italic>P<\/jats:italic> = 0.10) increase in risk of elevated in vivo frequencies of CA associated with the variant 312Asn allele in the total population. The relative risk was more pronounced in smokers (OR = 4.67; 95% CL = 1.04\u201320.90; <jats:italic>P<\/jats:italic> = 0.04) and in all subjects &gt;48 years old (OR = 7.33; 95% CL = 1.53\u201335.10; <jats:italic>P<\/jats:italic> = 0.01). Similarly, elevations in NNK\u2010induced aberrations were significantly associated with the 312Asn allele (OR = 3.69; 95% CL = 1.29\u201310.56; <jats:italic>P<\/jats:italic> = 0.02). The risk was higher in smokers (OR = 4.62; 95% CL = 1.14\u201318.70; <jats:italic>P<\/jats:italic> = 0.04) and in subjects &gt;48 years old (OR = 5.76; 95% CL = 1.30\u201325.41; <jats:italic>P<\/jats:italic> = 0.03). No significant effect was observed with the 715Gln variant allele in relation to either in vivo or NNK\u2010induced CA. These data suggest that the Asp312Asn polymorphism may alter the phenotype of the XPD protein, resulting in reduced DNA\u2010repair capacity. Environ. Mol. Mutagen. 44:65\u201373, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.20032","type":"journal-article","created":{"date-parts":[[2004,6,11]],"date-time":"2004-06-11T07:00:49Z","timestamp":1086937249000},"page":"65-73","source":"Crossref","is-referenced-by-count":37,"title":["Effect of <i>XPD\/ERCC2<\/i> polymorphisms on chromosome aberration frequencies in smokers and on sensitivity to the mutagenic tobacco\u2010specific nitrosamine NNK"],"prefix":"10.1002","volume":"44","author":[{"given":"Alessandra A.","family":"Affatato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Wolfe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirtha S.","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Csilla","family":"Hallberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinel M.","family":"Ammenheuser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherif Z.","family":"Abdel\u2010Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,6,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(00)00532-2"},{"key":"e_1_2_1_3_1","first-page":"1","article-title":"Role of CYP2E1 and CYP2D6 allelic variants in NNK\u2010induced chromosome aberration","volume":"10","author":"Abdel\u2010Rahman SZ","year":"1999","journal-title":"Pharmacogenetics"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.3.415"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.10142"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20012"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.011091249"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/17.1.56"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0921-8734(95)00017-Z"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/17.6.463"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.11.874"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(94)00131-T"},{"key":"e_1_2_1_13_1","first-page":"1619","article-title":"Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens","volume":"60","author":"Bonassi S","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.8.530"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4997"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/2491"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/es960920a"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(00)00059-8"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.5.965"},{"key":"e_1_2_1_20_1","first-page":"77","article-title":"Polymorphisms in the DNA repair gene XPD: correlations with risk and age at onset of basal cell carcinoma","volume":"8","author":"Dybdahl M","year":"1999","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1161(75)90082-5"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(86)90082-0"},{"key":"e_1_2_1_23_1","first-page":"2919","article-title":"Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage","volume":"54","author":"Hagmar L","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_1_24_1","first-page":"4117","article-title":"Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH)","volume":"58","author":"Hagmar L","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx980005y"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.8.1185"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.4.599"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910430310"},{"key":"e_1_2_1_29_1","first-page":"1","article-title":"An international system for human cytogenetic nomenclature. 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