title: Sulfotransferase 1A1 and glutathione S-transferase P1 genetic polymorphisms modulate the levels of urinary 8-hydroxy-2'-deoxyguanosine in betel quid chewers.
abstract: Betel quid chewing has been associated with several human cancers. However, the role of betel quid in carcinogenesis remains uncertain. Piper betel contains high concentrations of safrole (an inducer of DNA oxidative damage). Safrole may be metabolized by hepatic sulfotransferase 1A1 (SULT1A1), or glutathione S-transferases (GSTM1, GSTT1, and GSTP1). Thus, we investigated the association of genetic polymorphisms of SULT1A1, GSTM1, GSTT1, and GSTP1 with DNA oxidative damage among betel quid chewers. A biomarker for oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) level, was analyzed using isotope-dilution LC-MS/MS in 64 betel quid chewers and 129 non-betel quid chewers. Data on demographics and habits (smoking, alcohol drinking, and betel quid chewing) were obtained from questionnaires. Our results revealed that urinary 8-OHdG level was higher in chewers with SULT1A1 Arg-His genotype than in chewers with SULT1A1 Arg-Arg genotype. Urinary 8-OHdG level was also higher in chewers with GSTP1 Ile-Ile genotype. Furthermore, the combined effect of SULT1A1 and GSTP1 genotypes on urinary 8-OHdG was evaluated. Non-chewers with both SULT1A1 Arg-Arg and GSTP1 Val-Val/Ile-Val (reference group) had the lowest mean level (3.6 ng/mg creatinine), whereas chewers with either SULT1A1 Arg-His or GSTP1 Ile-Ile had the highest 8-OHdG mean level (6.2 ng/mg creatinine; vs. reference group, P = 0.04). Chewers with both of SULT1A1 Arg-Arg and GSTP1 Val-Val/Ile-Val (4.6 ng/mg creatinine), and non-chewers with either SULT1A1 Arg-His or GSTP1 Ile-Ile (4.7 ng/mg creatinine) had a moderately increased 8-OHdG level. Thus, the susceptible SULT1A1 and GSTP1 genotypes may modulate increased DNA oxidative stress elicited by betel-quid chewing.
authors.affiliation: Department of Public Health, College of Health Care and Management, Chung Shan Medical University, No. 110 Chien-Kuo N. Road Sec. 1, Taichung, Taiwan. rueyhong@csmu.edu.tw
authors.forename: Ruey-Hong
authors.initials: RH
authors.lastname: Wong
authors.forename: Chiung-Wen
authors.initials: CW
authors.lastname: Hu
authors.forename: Ching-Ying
authors.initials: CY
authors.lastname: Yeh
authors.forename: Mu-Rong
authors.initials: MR
authors.lastname: Chao
authors.forename: Chin-Chun
authors.initials: CC
authors.lastname: Chen
authors.forename: Jun-Huang
authors.initials: JH
authors.lastname: Huang
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Chang
authors.forename: Shin-I
authors.initials: SI
authors.lastname: Lee
authors.forename: Hong-Shen
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015239:Arylsulfotransferase / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D031721:Piper betle; D011110:Polymorphism, Genetic; D013624:Taiwan
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D005982:Glutathione Transferase; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D003849:Deoxyguanosine