Association of metabolic sulfotr

Association of metabolic sulfotransferase 1A1 and glutathione S-transferase P1 genetic polymorphisms with urinary 8-hydroxy-2’-deoxyguanosine in Taiwanese betel quid chewers

Shin-I Lee¹, Yuh-Hwu Chiou¹, Yu-Ling Li¹, Tun-Jen Hsiao², Ruey-Hong Wong¹

^1.Department of Public Health, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan.

^2.Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan.

Abstract

Betel-quid chewing has been reported to be associated with several human cancers in recent epidemiological studies. However, the role of betel-quid on the carcinogenesis remains indistinct. Piper betle contains high concentrations of safrole, which has been suggested to induce the formation of oxidative stress. Safrole may be metabolized by hepatic sulfotransferase 1A1 (SULT1A1), or glutathione S-transferases (GSTM1, GSTT1, and GSTP1), however, for human SULT1A1, GSTM1, GSTT1, and GSTP1, little is known about the effects of betel-quid chewing on their corresponding genetic polymorphisms and oxidative stress. Thus, we designed a population-based cross-sectional study to investigate the association of metabolic genetic polymorphisms and oxidative stress among betel-quid chewers. Study subjects comprised 27 current betel-quid chewers and 55 non-betel quid chewers (aged 21-69 years). Questionnaires were administered to obtain demographic data, cigarette-smoking, alcohol drinking, and betel-quid chewing habits. As a biomarker for oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels was analyzed with an enzyme-linked immunosorbent assay kit. The genotypes of SULT1A1, GSTM1, GSTT1, and GSTP1 were identified by polymerase chain reaction (PCR). Our result revealed that no statistical differences from urinary 8-OHdG were observed for those with different SULT1A1, GSTM1, GSTT1, GSTP1 genotypes among non-betel quid chewers. Interestingly, current betel-quid chewers possessing SULT1A1 Arg/His (50.8 vs. 11.5; P < 0.01) or GSTP1 Val/Val (22.8 vs. 10.1; P < 0.04) genotypes had significantly increased urinary 8-OHdG levels than did those with SULT1A1 Arg/Arg or GSTP1 Ile/Ile and Ile/Val genotypes. These results suggest that individuals with the susceptible metabolic SULT1A1 and GSTP1 genotypes may experience an increased DNA oxidative stress elicited by betel-quid chewing.

KEY WORDS: Betel-quid chewing; safrole; SULT1A1 gene; GSTP1 gene; urinary 8-hydroxy-2'-deoxyguanosine.