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Genetic Polymorphisms of SULT1A1 and SULT1E1 and the Risk and Survival of Breast Cancer

Departments of ¹ Preventive Medicine, ² Surgery, and ³ Pharmacology, Seoul National University College of Medicine; ⁴ Cancer Research Institute; ⁵ Graduate School of Public Health, Seoul National University, Seoul, Korea; ⁶ Department of Preventive Medicine, Kon-Kuk University College of Medicine, Chungcheongbuk-Do, Korea; ⁷ Department of Surgery, Ulsan University College of Medicine, Seoul, Korea; ⁸ Department of Obstetrics and Gynecology, Ewha Womans University College of Medicine, Seoul, Korea; and ⁹ Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland

Requests for reprints: Daehee Kang, Department of Preventive Medicine, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799, Korea. Phone: 82-2-740-8326; Fax: 82-2-747-4830. E-mail: dhkang{at}snu.ac.kr

We examined whether common single nucleotide polymorphisms (SNP) in SULT1A1 (c.779G>A, *14A>G, and *85C>T) and SULT1E1 (IVS1-447C>A, IVS4-1653T>C, and *959G>A) genes influenced the risk and survival of breast cancer. Our study population consisted of 989 histologically confirmed sporadic breast cancer patients and 1,054 controls without history of cancer recruited from three teaching hospitals in Seoul. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression model. In the survival analysis for 529 breast cancer patients with completed treatments, the hazard ratios (HR) were calculated with Cox proportional hazard model. Women with the SULT1E1 *959 GA/AA genotype had a moderately decreased breast cancer risk compared with those with the GG genotypes (OR, 0.8; 95% CI, 0.70-1.00). When the haplotypes were considered, the homozygous *959 AA genotype together with the IVS4-1653 T>C base change (CTA-CCA haplotype) was associated with halved breast cancer risk (OR, 0.5; 95% CI, 0.24-0.88) compared with the wild type CTG-CTG haplotype. No other significant overall association was observed between the SULT1A1 and SULT1E1 SNPs nor haplotypes and breast cancer risk. When stratified by survival, patients with the SULT1E1 IVS4-1653 TC/CC genotypes showed a >3-fold risk of recurrence (HR, 3.2; 95% CI, 1.39-7.48) compared with those with the TT genotype. Moreover, when the haplotypes were considered, the SULT1E1 *959 G>A base change together with the IVS4-1653 T>C base change (CTG-CCA haplotype) was associated with a >4-fold risk of breast cancer (OR, 4.2; 95% CI, 1.15-15.15). These findings suggest that genetic polymorphisms of SULT1E1 are associated with increased risk and a disease free survival of breast cancer in Korean women.

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