Carcinogenesis Advance Access published online on January 6, 2009
Carcinogenesis, doi:10.1093/carcin/bgn283
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Sulfotransferase 1A1 Haplotypes Associated with Oral Squamous Cell Carcinoma Susceptibility in Male Taiwanese
1 Institute of Pharmacology
2 Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang-Ming University, Taipei
3 Department of Public Health, Chang Gung University
4 Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan
5 Department of Public Health, National Defense Medical Center, Taipei
6 Department of Medical Research & Education, Taipei Veterans General Hospital, Taiwan
7 National Research Institute of Chinese Medicine, Taipei
* To whom correspondence should be addressed: Tsung-Yun Liu, PhD, Institute of Environmental and Occupational Health, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Li-Nun St., Taipei, Taiwan, Fax: +886-2-2875-1562, Phone: +886-2-2874-7848, E-mail: tyliu{at}vghtpe.gov.tw
We have previously demonstrated that betel quid containing safrole induced DNA adducts are highly associated with the development of oral squamous cell carcinoma (OSCC) in Taiwan. Sulfotransferase is essential for the formation of these adducts. To elucidate the effects of SULT1A1 haplotypes on OSCC susceptibility, 160 male OSCC cases and 218 age- and sex-matched controls were screened for single nucleotide polymorphisms within the coding region of SULT1A1 by sequencing. We found that 445C>T (His149Tyr) and 507C>T polymorphisms were significantly associated with increased risk of OSCC. Based on the genotype analysis, haplotypes were constructed for 445C>T (His149Tyr), 507C>T, 600G>C and 638G>A (Arg213His) using GENECOUNTING software. After adjustment for age, cigarette smoking and betel quid chewing, we found that haplotype c containing 445C>T (His149Tyr), 507C>T, or 600G>C but not 638G>A (Arg213His) variant was significantly associated with increased risk of OSCC (OR, 3.24; 95% CI, 1.57-6.68) when compared to the haplotype a (wild-type). We analyzed the activity in sulfonation of 2-naphthol and 1'-hydroxysafrole of recombinant His149Tyr (445C>T) variant, which led to 51 % and 33 % reduced activity, respectively; Arg213His (638G>A) variant led to 72 % and 54 % reduced activity, respectively when compared to the wild-type. Taken together, haplotype analysis provides a novel evaluation of the SULT1A1 gene as a risk modifier on environmental carcinogen in OSCC and the association of SULT1A1 haplotypes with the risk of OSCC might be modified by betel quid chewing.
Key Words: betel quid • haplotype • OSCC • SNP • sulfotransferase 1A1
Received May 28, 2008; revised November 28, 2008; accepted December 3, 2008.