{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:38:44Z","timestamp":1788521924375,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,1,21]],"date-time":"2003-01-21T00:00:00Z","timestamp":1043107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2003,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cancer risk can be influenced by the exposure to endogenous or environmental toxins. Polymorphic enzymes involved in the metabolic activation\/detoxification of carcinogens may account for individual variations of risk. We studied the polymorphisms of five enzymes of the P450 superfamily, <jats:italic>CYP1A1<\/jats:italic>, <jats:italic>CYP1A2<\/jats:italic>, <jats:italic>CYP2D6<\/jats:italic>, <jats:italic>CYP2E1<\/jats:italic> and <jats:italic>CY3A4<\/jats:italic>, as risk factors for liver disease progression and cancer in hepatitis C virus\u2010infected patients. CYP genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism or allele\u2010specific PCR. Different stages of disease were considered, as follows: 90 asymptomatic carriers and 87 chronic hepatitis, 92 cirrhosis and 91 hepatocellular carcinoma (HCC) cases. Reference allele frequencies were obtained from 99 blood donors. Allele distributions among categories were compared using the \u03c7<jats:sup>2<\/jats:sup> test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to express relative risks. Independent associations were modeled by correspondence analysis and logistic regression. Frequencies of the <jats:italic>CYP1A1<\/jats:italic> highly inducible alleles, <jats:italic>MspI<\/jats:italic> m2 and <jats:italic>Val<\/jats:italic>, were increased in liver disease patients compared with carriers; no specific association with HCC was found. The high\u2010activity <jats:italic>CYP2E1<\/jats:italic> c2 allele was underrepresented among HCC patients with respect to other HCV categories, including cirrhosis. CYP2D6 poor metabolizer (PM) genotypes were significantly more frequent in healthy subjects (7.1%) and carriers (11.1%) than in hepatitis\/cirrhosis (4.6%) and HCC (1.2%) patients. This was confirmed by multivariable analysis. PM genotypes protected against progressive disease as ORs reduced proportionally to stage. The age at diagnosis for HCC was anticipated in non\u2010PM individuals. No differences were seen for <jats:italic>CYP1A2<\/jats:italic> and <jats:italic>CYP3A4<\/jats:italic> genes. Polymorphic variants of CYP genes may contribute to the progression of liver disease and HCC risk in HCV\u2010infected subjects. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10937","type":"journal-article","created":{"date-parts":[[2003,2,6]],"date-time":"2003-02-06T01:52:07Z","timestamp":1044496327000},"page":"310-317","source":"Crossref","is-referenced-by-count":52,"title":["CYP enzyme polymorphisms and susceptibility to HCV\u2010related chronic liver disease and liver cancer"],"prefix":"10.1002","volume":"104","author":[{"given":"Laura","family":"Silvestri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Sonzogni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"De 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