Abstract
Sulfotransferase 1A1, an important member of sulfotransferase superfamily, is involved in the biotransformation of many compounds including tobacco carcinogens. A single nucleotide polymorphism (G638A) in the sulfotransferase 1A1 (SULT1A1) gene causes Arg213His amino acid change and consequently results in significantly reduced enzyme activity and thermostability. We thus hypothesized that the variant SULT1A1 allele may protect against the risk of lung cancer related to tobacco smoking. To examine this hypothesis, we analyzed 805 patients with lung cancer and 809 controls for this polymorphism in a hospital-based, case-control study. We observed that, compared with the GG genotype, the variant SULT1A1 genotype (638GA or AA) was associated with a significantly increased risk for overall lung cancer [odds ratio (OR) 1.85; 95% confidence interval (CI) 1.44-2.37]. Stratification analysis showed that the increased risk of lung cancer related to the variant SULT1A1 genotypes was more pronounced in younger subjects and limited to smokers but not non-smokers [OR 2.28 (95% CI 1.66-3.13) versus OR 1.35 (95% CI 0.91-1.99); P for homogeneity = 0.000]. Furthermore, the risk of lung cancer for the variant genotypes was increased consistently with cumulative smoking dose, with the ORs being 1.66 (95% CI, 0.75-3.68), 2.28 (95% CI, 1.47-3.54) and 3.35 (95% CI, 1.71-6.57) for those who smoked <15 pack-years, 15-36 pack-years and >36 pack-years, respectively (P for trend = 0.000). When analysis was stratified by histological subtypes of lung cancer, consistent results were observed for all three major types of the cancer, i.e. squamous cell carcinoma, adenocarcinoma and other types. Our results, which are against the original hypothesis, demonstrate that the variant SULT1A1 638A allele is associated with susceptibility to lung cancer in relation to tobacco smoking.
