Genetic polymorphisms of steroid hormone metabolizing enzymes and risk of liver cancer in hepatitis C-infected patients

Laura Rossi, Michela Leveri, Chiara Gritti, Annalisa De Silvestri, Claudio Zavaglia, Laura Sonzogni, Laura Silvestri, Emilio Civardi, Mario U. Mondelli, Enrico M. Silini

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background/Aims: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5α-reductase type II (SRD5A2), cytochrome P450c17α (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease. Methods: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category. Results: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2%, odds ratio (OR): 2.29, P: 0.05). Females mostly contributed to this association (OR: 4.95, P: 0.01) and OR values increased in post-menopausal women (OR: 6.00, P: 0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms. Conclusions: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.

Original languageEnglish
Pages (from-to)564-570
Number of pages7
JournalJournal of Hepatology
Volume39
Issue number4
DOIs
Publication statusPublished - Oct 1 2003

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Genetic Polymorphisms
Cytochromes
Liver Neoplasms
Hepatitis C
Catechol O-Methyltransferase
Odds Ratio
Steroids
Hepacivirus
Hormones
Enzymes
Androgens
Hepatocellular Carcinoma
Estrogens
Chronic Hepatitis C
Restriction Fragment Length Polymorphisms
Hepatitis
Liver Diseases
Healthy Volunteers
Oxidoreductases
Fibrosis

Keywords

  • Chronic liver disease
  • DNA polymorphism
  • Genetic susceptibility
  • Hepatocellular carcinoma
  • Hormone regulatory gene

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Genetic polymorphisms of steroid hormone metabolizing enzymes and risk of liver cancer in hepatitis C-infected patients. / Rossi, Laura; Leveri, Michela; Gritti, Chiara; De Silvestri, Annalisa; Zavaglia, Claudio; Sonzogni, Laura; Silvestri, Laura; Civardi, Emilio; Mondelli, Mario U.; Silini, Enrico M.

In: Journal of Hepatology, Vol. 39, No. 4, 01.10.2003, p. 564-570.

Research output: Contribution to journalArticle

Rossi, Laura ; Leveri, Michela ; Gritti, Chiara ; De Silvestri, Annalisa ; Zavaglia, Claudio ; Sonzogni, Laura ; Silvestri, Laura ; Civardi, Emilio ; Mondelli, Mario U. ; Silini, Enrico M. / Genetic polymorphisms of steroid hormone metabolizing enzymes and risk of liver cancer in hepatitis C-infected patients. In: Journal of Hepatology. 2003 ; Vol. 39, No. 4. pp. 564-570.
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abstract = "Background/Aims: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5α-reductase type II (SRD5A2), cytochrome P450c17α (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease. Methods: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category. Results: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2{\%}, odds ratio (OR): 2.29, P: 0.05). Females mostly contributed to this association (OR: 4.95, P: 0.01) and OR values increased in post-menopausal women (OR: 6.00, P: 0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms. Conclusions: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.",
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T1 - Genetic polymorphisms of steroid hormone metabolizing enzymes and risk of liver cancer in hepatitis C-infected patients

AU - Rossi, Laura

AU - Leveri, Michela

AU - Gritti, Chiara

AU - De Silvestri, Annalisa

AU - Zavaglia, Claudio

AU - Sonzogni, Laura

AU - Silvestri, Laura

AU - Civardi, Emilio

AU - Mondelli, Mario U.

AU - Silini, Enrico M.

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Background/Aims: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5α-reductase type II (SRD5A2), cytochrome P450c17α (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease. Methods: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category. Results: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2%, odds ratio (OR): 2.29, P: 0.05). Females mostly contributed to this association (OR: 4.95, P: 0.01) and OR values increased in post-menopausal women (OR: 6.00, P: 0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms. Conclusions: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.

AB - Background/Aims: Genetic polymorphisms of enzymes involved in hormone metabolism can influence hormonal activities and risk of hormone-dependent cancers. As progression of chronic hepatitis C and risk of liver cancer is higher in males than in females, we evaluated whether the polymorphisms of three enzymes participating in the pathway of estrogen and androgen biosynthesis and inactivation, 5α-reductase type II (SRD5A2), cytochrome P450c17α (CYP17) and catechol-O-methyltransferase (COMT), might affect the expression of hepatitis C virus (HCV)-related liver disease. Methods: The study included 78 healthy subjects and 387 HCV patients: 100 asymptomatic carriers, 105 hepatitis, 90 cirrhosis and 92 hepatocellular carcinomas (HCC). Variant positions SRD5A2 V89L and A49T, CYP17 (-34)T/C and COMT V108M were analysed by polymerase chain reaction and restriction fragment length polymorphism. A cross-sectional study of association was performed, considering carriers as reference category. Results: The CYP17 (-34)C/C genotype was over-represented in HCC patients as compared to carriers (22.5 vs. 11.2%, odds ratio (OR): 2.29, P: 0.05). Females mostly contributed to this association (OR: 4.95, P: 0.01) and OR values increased in post-menopausal women (OR: 6.00, P: 0.03). No differences were observed for SRD5A2 and COMT gene polymorphisms. Conclusions: CYP17 high-activity alleles associated with increased circulating levels of estrogens and androgens may affect liver cancer risk in HCV-infected women.

KW - Chronic liver disease

KW - DNA polymorphism

KW - Genetic susceptibility

KW - Hepatocellular carcinoma

KW - Hormone regulatory gene

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