{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:29:13Z","timestamp":1786418953309,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alcohol\u2010dependent (AD) patients frequently present with a history of alcohol\u2010related cancers, but the timing of cancer treatment relative to the onset of advanced alcohol use disorder and the role of\n                      <jats:italic>ADH1B<\/jats:italic>\n                      \/\n                      <jats:italic>ALDH2<\/jats:italic>\n                      genotypes remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We reviewed cancer histories at the initial visit of 5214 Japanese male AD patients (mean age 53.3\u2009[SD\u200911.9] years), all genotyped for\n                      <jats:italic>ADH1B<\/jats:italic>\n                      (rs1229984) and\n                      <jats:italic>ALDH2<\/jats:italic>\n                      (rs671). Multiple logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for site\u2010specific cancers, using fast\u2010metabolizing\n                      <jats:italic>ADH1B*2<\/jats:italic>\n                      and active\n                      <jats:italic>ALDH2*1\/*1<\/jats:italic>\n                      as the reference.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Alcohol\u2010related cancers were reported in 385 patients (7.38%): head and neck cancer (HNC) 1.05%, esophageal cancer (EC) 1.40%, gastric cancer (GC) 3.91%, colorectal cancer (CRC) 1.53%, and liver cancer (LC) 0.59%. Surgical treatment rates were high across sites. Most cancers were treated during or after the onset of advanced alcohol use disorder (HNC 81.8%, EC 74.0%, GC 48.5%, CRC 63.8%, and LC 87.1%). The slow\u2010metabolizing\n                      <jats:italic>ADH1B*1\/*1<\/jats:italic>\n                      genotype was associated with high ORs for HNC (1.99; 95% CI 1.14\u20133.47) and EC (3.05; 1.87\u20134.99), but low ORs for GC (0.65; 0.45\u20130.95) and gastrectomy for peptic ulcer disease (0.59; 0.38\u20130.92). Gastrectomy, common among GC cases, accelerates alcohol delivery to the small intestine, increasing peak blood alcohol levels and exposure, and may offset the AD risk associated with\n                      <jats:italic>ADH1B*1\/*1<\/jats:italic>\n                      . The inactive\n                      <jats:italic>ALDH2*2<\/jats:italic>\n                      allele conferred elevated ORs for HNC (8.63; 4.90\u201315.21), EC (11.35; 6.78\u201318.99), GC (1.54; 1.08\u20132.19), and CRC (1.72; 1.01\u20132.91). The combined genotype (\n                      <jats:italic>ADH1B*1\/*1<\/jats:italic>\n                      and\n                      <jats:italic>ALDH2*2<\/jats:italic>\n                      ) substantially increased ORs for HNC (17.05; 8.17\u201335.59) and EC (35.03; 17.38\u201370.65). Multiorgan cancerization was common along the digestive tract. The combined genotype increased ORs for multiorgan cancerization in HNC and EC, and\n                      <jats:italic>ALDH2*2<\/jats:italic>\n                      increased ORs in GC and CRC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Genotype strongly influences alcohol\u2010related cancer risk, and many cancers occur during or after advanced alcohol use disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72092","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:43:17Z","timestamp":1783482197000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["History of Alcohol\u2010Related Cancers and\n                    <i>ADH1B\/ALDH2<\/i>\n                    Genotypes in a Large Japanese Cohort of Male Patients With Alcohol Dependence"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-1359","authenticated-orcid":false,"given":"Akira","family":"Yokoyama","sequence":"first","affiliation":[{"name":"National Hospital Organization Kurihama Medical and Addiction Center  Yokosuka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Health Promotion National Institute of Public Health  Wako Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Alcohol Consumption and Ethyl Carbamate","author":"International Agency for Research on Cancer","year":"2010"},{"key":"e_1_2_11_3_1","first-page":"30","volume-title":"Diet, Nutrition, Physical Activity and Stomach Cancer 2016, Revised 2018","author":"World Cancer Research Fund International","year":"2018"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2737"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agw071"},{"issue":"1","key":"e_1_2_11_6_1","first-page":"1","article-title":"Esophageal Cancer and Multiple Primary Cancer","volume":"24","author":"Makuuchi H.","year":"1997","journal-title":"Gan to Kagaku Ryoho. 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