Carcinogenesis Advance Access published online on December 19, 2003
Carcinogenesis, doi:10.1093/carcin/bgh053
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
* Corresponding author. E-mail: dlin{at}public.bta.net.cn.
Received 21 October 2003
; revised 4 December 2003
; accepted 8 December 2003
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 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 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 nonsmokers [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, 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.
SULT1A1, genetic polymorphism, lung cancer, molecular epidemiology
A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking
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