CYP17 polymorphism and tamoxifen-induced hepatic steatosis.

CYP17 polymorphism and tamoxifen-induced hepatic steatosis. Research Abstract Details 

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CYP17 polymorphism and tamoxifen-induced hepatic steatosis. Abstract Text:

Takenao Ohnishi,Yasuhiro Ogawa,Toshiji Saibara,Akihito Nishioka,Shinji Kariya,Mitsutaka Fukumoto,Saburo Onishi,Shoji Yoshida,

Hepatic steatosis is a frequent complication, which sometimes develops nonalcoholic steatohepatitis (NASH), in breast cancer patients treated with tamoxifen, a potent antagonist of estrogen. Recently we reported the impairment of fatty acid beta-oxidation and the enhancing fatty infiltration to hepatocytes in aromatase deficiency (ArKO) mice as the estrogen deficiency models. This experimental observation let us speculate strong link between estrogen and hepatic steatosis. In this study, we investigated whether a polymorphism in the cytochrome P450c17alpha gene (CYP17), which is associated with circulating estrogen levels, influences the development of tamoxifen-induced hepatic steatosis. This consecutive study included 180 breast cancer patients undergoing tamoxifen treatment. Genomic DNA extracted from the peripheral blood of each patient was analyzed by restriction fragment length polymorphism (defined as the A1 and A2 alleles). The extent of hepatic steatosis was assessed by computed tomography (CT) as the liver/spleen (L/S) ratio. While receiving adjuvant tamoxifen, 57 of 180 patients developed hepatic steatosis (L/S ratio <0.9) without obvious changes in body mass index (BMI). We observed a significant association between the A2/A2 genotype and the development of hepatic steatosis compared with the A1/A1 genotype [odds ratio (OR), 3.60; 95% confidence interval (C.I.)=1.42-9.10]. The A1/A2 genotype was at an intermediately increased risk of hepatic steatosis (OR, 2.24; 95% C.I.=0.99-5.08). The presence of the A2 allele possibly increased the progression of hepatic steatosis with a gene dosage effect (P=0.06). Our results suggest that functional polymorphism in CYP17 may be involved in determining susceptibility of tamoxifen-induced hepatic steatosis.

CYP17 polymorphism and tamoxifen-induced hepatic steatosis. Publishing Authors By Initials

T Ohnishi,Y Ogawa,T Saibara,A Nishioka,S Kariya,M Fukumoto,S Onishi,S Yoshida,

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CYP17 polymorphism and tamoxifen-induced hepatic steatosis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hepatology research : the official journal of the

VOLUME: 33

Page Numbers: 178-80

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ISSN: 1386-6346

DAY: 7

MONTH: Oct

YEAR: 2005

CYP17 polymorphism and tamoxifen-induced hepatic steatosis. Information

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LANGUAGE: eng

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Grant and Affiliation Information for CYP17 polymorphism and tamoxifen-induced hepatic steatosis.

AFFILIATION: Department of Tumor Radiology, Kochi Medical School, Kohau, Okoh-cho, Nankoku-shi, Kochi 783-8505, Japan.

Country: Netherlands

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MEDLINETA: Hepatol Res

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