Skip to main content

Advertisement

SpringerLink
Log in

Modifying Effects of Sulfotransferase 1A1 Gene Polymorphism on the Association of Breast Cancer Risk with Body Mass Index or Endogenous Steroid Hormones

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Sulfotransferase (SULT) 1A1 is involved in the inactivation and elimination of estrogens and catechol estrogens. A common functional polymorphism (Arg213His) has been linked in our previous study of postmenopausal Caucasian women to an elevated risk of breast cancer and the association appeared to be modified by factors related to high endogenous estrogen exposures. We further evaluated this polymorphism and levels of BMI and steroid hormones in association with breast cancer risk in a population-based case–control study of Chinese women, involving 1102 incident cases aged 25–64 years and 1147 age-matched population controls. The SULT1A1 genotype was not associated with overall breast cancer risk in this population. A possible association was suggested for postmenopausal breast cancer (adjusted odds ratio [OR] = 1.4, 95% CI  = 0.9–2.1 for subject carrying the variant His allele). The SULT1A1 genotype was found to significantly modify postmenopausal breast cancer risk associated with a high BMI (≥25 kg/m2) (p for interaction = 0.02), with an adjusted OR of 3.6 (95% CI  = 1.5–8.7) for women with the Arg/His genotype compared with 1.1 (0.8–1.5) for women with the Arg/Arg genotype (no His/His genotype was identified in this study population). Similarly, the risk associated with a long duration (≥30 years) of menstruation also substantially differed by the SULT1A1 genotype (p for interaction = 0.05), with an OR of 4.0 (95% CI  = 1.3–12.8) for women with the Arg/His genotype and 1.4 (0.8–2.5) for women with the Arg/Arg genotype. Positive associations with blood levels of steroid hormones were also found generally to be more pronounced among women carrying the His allele. No similar effect modification was found for premenopausal breast cancer, however. These data suggest that the SULT1A1 Arg213His polymorphism may modify the effect of endogenous sex hormone exposures on postmenopausal breast cancer risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BMI:

body mass index

CI:

confidence interval

DHEA-S:

dehydroepiandrosterone sulfate

estrone-S:

estrone sulfate

OR:

odds ratio

SNP:

single nucleotide polymorphism

SHBG:

sex hormone-binding globulin

SULT:

sulfotransferase

References

  1. M Clemons P Goss (2001) ArticleTitleEstrogen and the risk of breast cancer N Engl J Med 344 276–285 Occurrence Handle10.1056/NEJM200101253440407 Occurrence Handle11172156 Occurrence Handle1:CAS:528:DC%2BD3MXht1Sruro%3D

    Article  PubMed  CAS  Google Scholar 

  2. FF Parl (2000) Estrogens as breast cancer risk factor FF Parl (Eds) Estrogens, Estrogen Receptor and Breast Cancer IOS Press Amsterdam Netherlands 205–242

    Google Scholar 

  3. CJ Gruber W Tschugguel C Schneeberger JC Huber (2002) ArticleTitleProduction and actions of estrogens N Engl J Med 346 340–352 Occurrence Handle10.1056/NEJMra000471 Occurrence Handle11821512 Occurrence Handle1:CAS:528:DC%2BD38XpsVykug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  4. Glatt H, Meinl W: Pharmacogenetics of soluble sulfotransferases (SULTs). Naunyn Schmiedebergs. Arch Pharmacol (online publication), 2003, Nov 5

  5. RM Weinshilboum DM Otterness IA Aksoy TC Wood C Her RB Raftogianis (1997) ArticleTitleSulfation and sulfotransferases 1: sulfotransferase molecular biology: cDNAs and genes FASEB J 11 3–14 Occurrence Handle9034160 Occurrence Handle1:CAS:528:DyaK2sXhtFaks7Y%3D

    PubMed  CAS  Google Scholar 

  6. CN Falany (1997) ArticleTitleEnzymology of human cytosolic sulfotransferases FASEB J 11 206–216 Occurrence Handle9068609 Occurrence Handle1:CAS:528:DyaK2sXhvVGmtLw%3D

    PubMed  CAS  Google Scholar 

  7. MW Coughtrie (2002) ArticleTitleSulfation through the looking glass – recent advances in sulfotransferase research for the curious Pharmacogenomics J 2 297–308 Occurrence Handle10.1038/sj.tpj.6500117 Occurrence Handle12439736 Occurrence Handle1:CAS:528:DC%2BD38Xoslaks7s%3D

    Article  PubMed  CAS  Google Scholar 

  8. RB Raftogianis TC Wood DM Otterness JA Loon ParticleVan RM Weinshilboum (1997) ArticleTitlePhenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype Biochem Biophys Res Commun 239 298–304 Occurrence Handle10.1006/bbrc.1997.7466 Occurrence Handle9345314 Occurrence Handle1:CAS:528:DyaK2sXmvVKmt7k%3D

    Article  PubMed  CAS  Google Scholar 

  9. RB Raftogianis TC Wood RM Weinshilboum (1999) ArticleTitleHuman phenol sulfotransferases SULT1A2 and SULT1A1: genetic polymorphisms, allozyme properties, and human liver genotype–phenotype correlations Biochem Pharmacol 58 605–616 Occurrence Handle10.1016/S0006-2952(99)00145-8 Occurrence Handle10413297 Occurrence Handle1:CAS:528:DyaK1MXks1WrsLw%3D

    Article  PubMed  CAS  Google Scholar 

  10. MW Coughtrie RA Gilissen B Shek RC Strange AA Fryer PW Jones DE Bamber (1999) ArticleTitlePhenol sulphotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations Biochem J 337 45–49 Occurrence Handle10.1042/0264-6021:3370045 Occurrence Handle9854023 Occurrence Handle1:CAS:528:DyaK1MXjslaltA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  11. W Zheng D Xie JR Cerhan TA Sellers W Wen AR Folsom (2001) ArticleTitleSulfotransferase 1A1 polymorphism, endogenous estrogen exposure, well-done meat intake, and breast cancer risk Cancer Epidemiol Biomarkers Prev 10 89–94 Occurrence Handle11219777

    PubMed  Google Scholar 

  12. D Tang A Rundle L Mooney S Cho F Schnabel A Estabrook A Kelly R Levine H Hibshoosh F Perera (2003) ArticleTitleSulfotransferase 1A1 (SULT1A1) polymorphism, PAH-DNA adduct levels in breast tissue and breast cancer risk in a case–control study Breast Cancer Res Treat 78 217–222 Occurrence Handle10.1023/A:1022968303118 Occurrence Handle12725421 Occurrence Handle1:CAS:528:DC%2BD3sXit1yqtL8%3D

    Article  PubMed  CAS  Google Scholar 

  13. M Saintot C Malaveille A Hautefeuille M Gerber (2003) ArticleTitleInteractions between genetic polymorphism of cytochrome P450-1B1, sulfotransferase 1A1, catechol-o-methyltransferase and tobacco exposure in breast cancer risk Int J Cancer 107 652–657 Occurrence Handle10.1002/ijc.11432 Occurrence Handle14520706 Occurrence Handle1:CAS:528:DC%2BD3sXoslCjs78%3D

    Article  PubMed  CAS  Google Scholar 

  14. DF Han X Zhou MB Hu CH Wang W Xie XD Tan F Zheng F Liu (2004) ArticleTitleSulfotransferase 1A1 (SULT1A1) polymorphism and breast cancer risk in Chinese women Toxicol Lett 150 167–177 Occurrence Handle10.1016/j.toxlet.2004.01.012 Occurrence Handle15093672 Occurrence Handle1:CAS:528:DC%2BD2cXjtF2rurk%3D

    Article  PubMed  CAS  Google Scholar 

  15. P Seth KL Lunetta DW Bell H Gray SM Nasser E Rhei CM Kaelin DJ Iglehart JR Marks JE Garber DA Haber K Polyak (2000) ArticleTitlePhenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer Cancer Res 60 6859–6863 Occurrence Handle11156380 Occurrence Handle1:CAS:528:DC%2BD3MXjsVKqsw%3D%3D

    PubMed  CAS  Google Scholar 

  16. C Lilla A Risch S Kropp J Chang-Claude (2005) ArticleTitleSULT1A1 genotype, active and passive smoking, and breast cancer risk by age 50 years in a German case–control study Breast Cancer Res 7 R229–R237 Occurrence Handle10.1186/bcr976 Occurrence Handle15743503 Occurrence Handle1:CAS:528:DC%2BD2MXhslGitLw%3D

    Article  PubMed  CAS  Google Scholar 

  17. EJ Carlini RB Raftogianis TC Wood F Jin W Zheng TR Rebbeck RM Weinshilboum (2001) ArticleTitleSulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects Pharmacogenetics 11 57–68 Occurrence Handle10.1097/00008571-200102000-00007 Occurrence Handle11207031 Occurrence Handle1:CAS:528:DC%2BD3MXhtFKhu7o%3D

    Article  PubMed  CAS  Google Scholar 

  18. W Zheng DW Xie F Jin JR Cheng Q Dai WQ Wen XO Shu YT Gao (2000) ArticleTitleGenetic polymorphism of cytochrome P450-1B1 and risk of breast cancer Cancer Epidemiol Biomarkers Prev 9 147–150 Occurrence Handle10698474 Occurrence Handle1:CAS:528:DC%2BD3cXitF2qtb4%3D

    PubMed  CAS  Google Scholar 

  19. G Yang G Lu F Jin Q Dai R Best XO Shu JR Chen XY Pan M Shrubsole W Zheng (2001) ArticleTitlePopulation-based, case–control study of blood C-peptide level and breast cancer risk Cancer Epidemiol Biomarkers Prev 10 1207–1211 Occurrence Handle11700270 Occurrence Handle1:CAS:528:DC%2BD3MXptFWqu7k%3D

    PubMed  CAS  Google Scholar 

  20. W Zheng YT Gao XO Shu W Wen Q Cai Q Dai JR Smith (2004) ArticleTitlePopulation-based case–control study of CYP11A gene polymorphism and breast cancer risk Cancer Epidemiol Biomarkers Prev 13 709–714 Occurrence Handle15159300 Occurrence Handle1:CAS:528:DC%2BD2cXkt1Ght70%3D

    PubMed  CAS  Google Scholar 

  21. H Yu XO Shu R Shi Q Dai F Jin YT Gao BD Li W Zheng (2003) ArticleTitlePlasma sex steroid hormones and breast cancer risk in Chinese women Int J Cancer 105 92–97 Occurrence Handle10.1002/ijc.11034 Occurrence Handle12672036 Occurrence Handle1:CAS:528:DC%2BD3sXjtVWrs78%3D

    Article  PubMed  CAS  Google Scholar 

  22. NE Breslow NE Day (1980) Statistical Methods in Cancer Research: Analysis of Case–control Studies (IARC Sci Publ 32) IARC Lyon, France

    Google Scholar 

  23. SL Zheng W Zheng BL Chang XO Shu Q Cai H Yu Q Dai J Xu YT Gao (2003) ArticleTitleJoint effect of estrogen receptor beta sequence variants and endogenous estrogen exposure on breast cancer risk in Chinese women Cancer Res 63 7624–7629 Occurrence Handle14633679 Occurrence Handle1:CAS:528:DC%2BD3sXptFOls7Y%3D

    PubMed  CAS  Google Scholar 

  24. YT Gao XO Shu Q Dai JD Potter LA Brinton W Wen TA Sellers LH Kushi Z Ruan RM Bostick F Jin W Zheng (2000) ArticleTitleAssociation of menstrual, reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study Int J Cancer 87 295–300 Occurrence Handle10.1002/1097-0215(20000715)87:2<295::AID-IJC23>3.0.CO;2-7 Occurrence Handle10861490 Occurrence Handle1:STN:280:DC%2BD3czps1Wgtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  25. K McPherson CM Steel JM Dixon (2000) ArticleTitleABC of breast diseases Breast cancer-epidemiology, risk factors, and genetics BMJ 321 624–628 Occurrence Handle10.1136/bmj.321.7261.624 Occurrence Handle10977847 Occurrence Handle1:STN:280:DC%2BD3cvmvF2luw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  26. TJ Key PK Verkasalo (1999) ArticleTitleEndogenous hormones and the aetiology of breast cancer Breast Cancer Res 1 18–21 Occurrence Handle10.1186/bcr7 Occurrence Handle11250677 Occurrence Handle1:CAS:528:DC%2BD3cXlsFKgs7c%3D

    Article  PubMed  CAS  Google Scholar 

  27. TJ Key PN Appleby GK Reeves A Roddam JF Dorgan C Longcope FZ Stanczyk HE Stephenson SuffixJr RT Falk R Miller A Schatzkin DS Allen IS Fentiman TJ Key DY Wang M Dowsett HV Thomas SE Hankinson P Toniolo A Akhmedkhanov K Koenig RE Shore A Zeleniuch-Jacquotte F Berrino P Muti A Micheli V Krogh S Sieri V Pala E Venturelli G Secreto E Barrett-Connor GA Laughlin M Kabuto S Akiba RG Stevens K Neriishi CE Land JA Cauley LH Kuller SR Cummings KJ Helzlsouer AJ Alberg TL Bush GW Comstock GB Gordon SR Miller C Longcope (2003) ArticleTitleEndogenous Hormones Breast Cancer Collaborative Group: Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women J Natl Cancer Inst 95 1218–1226 Occurrence Handle12928347 Occurrence Handle1:CAS:528:DC%2BD3sXntlWqsb8%3D Occurrence Handle10.1093/jnci/djg022

    Article  PubMed  CAS  Google Scholar 

  28. XO Shu F Jin Q Dai JR Shi JD Potter LA Brinton JR Hebert Z Ruan YT Gao W Zheng (2001) ArticleTitleAssociation of body size and fat distribution with risk of breast cancer among Chinese women Int J Cancer 94 449–455 Occurrence Handle10.1002/ijc.1487 Occurrence Handle11745429 Occurrence Handle1:CAS:528:DC%2BD3MXnsVersb0%3D

    Article  PubMed  CAS  Google Scholar 

  29. RJ Hung P Boffetta P Brennan C Malaveille A Hautefeuille F Donato U Gelatti M Spaliviero D Placidi A Carta A Scotto di Carlo S Porru (2004) ArticleTitleGST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population Int J Cancer 110 598–604 Occurrence Handle10.1002/ijc.20157 Occurrence Handle15122594 Occurrence Handle1:CAS:528:DC%2BD2cXktlKkur4%3D

    Article  PubMed  CAS  Google Scholar 

  30. U Langsenlehner P Krippl W Renner B Yazdani-Biuki T Eder G Wolf TC Wascher B Paulweber W Weitzer H Samonigg (2004) ArticleTitleGenetic variants of the sulfotransferase 1A1 and breast cancer risk Breast Cancer Res Treat 87 19–22 Occurrence Handle10.1023/B:BREA.0000041574.90735.ea Occurrence Handle15377847 Occurrence Handle1:CAS:528:DC%2BD2cXnsFOqtr8%3D

    Article  PubMed  CAS  Google Scholar 

  31. TC Cheng ST Chen CS Huang YP Fu JC Yu CW Cheng PE Wu CY Shen (2005) ArticleTitleBreast cancer risk associated with genotype polymorphism of the catechol estrogen-metabolizing genes: a multigenic study on cancer susceptibility Int J Cancer 113 345–353 Occurrence Handle10.1002/ijc.20630 Occurrence Handle15455371 Occurrence Handle1:CAS:528:DC%2BD2MXhsFSl

    Article  PubMed  CAS  Google Scholar 

  32. MT Wu YT Wang CK Ho DC Wu YC Lee HK Hsu EL Kao JM Lee (2003) ArticleTitleSULT1A1 polymorphism and esophageal cancer in males Int J Cancer 103 101–104 Occurrence Handle10.1002/ijc.10805 Occurrence Handle12455060 Occurrence Handle1:CAS:528:DC%2BD38Xptl2htrY%3D

    Article  PubMed  CAS  Google Scholar 

  33. G Liang X Miao Y Zhou W Tan D Lin (2004) ArticleTitleA functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking Carcinogenesis 25 773–778 Occurrence Handle10.1093/carcin/bgh053 Occurrence Handle14688021 Occurrence Handle1:CAS:528:DC%2BD2cXjsVekur4%3D

    Article  PubMed  CAS  Google Scholar 

  34. OJ Adegoke XO Shu YT Gao Q Cai J Breyer J Smith W Zheng (2004) ArticleTitleGenetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer Breast Cancer Res Treat 85 239–245 Occurrence Handle10.1023/B:BREA.0000025419.26423.b8 Occurrence Handle15111762 Occurrence Handle1:CAS:528:DC%2BD2cXjsVerurs%3D

    Article  PubMed  CAS  Google Scholar 

  35. KM Egan Q Cai XO Shu F Jin TL Zhu Q Dai YT Gao W Zheng (2004) ArticleTitleGenetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer: results from the Shanghai Breast Cancer Study and meta-analysis Cancer Epidemiol Biomarkers Prev 13 197–204 Occurrence Handle10.1158/1055-9965.EPI-03-0294 Occurrence Handle14973092 Occurrence Handle1:CAS:528:DC%2BD2cXhtleisrk%3D

    Article  PubMed  CAS  Google Scholar 

  36. JH Fowke XO Shu Q Dai F Jin Q Cai YT Gao W Zheng (2004) ArticleTitleOral contraceptive use and breast cancer risk: modification by NAD(P)H:quinine oxoreductase (NQO1) genetic polymorphisms Cancer Epidemiol Biomarkers Prev 13 1308–1315 Occurrence Handle15298951 Occurrence Handle1:CAS:528:DC%2BD2cXmtleksro%3D

    PubMed  CAS  Google Scholar 

  37. W Wen Q Cai XO Shu JR Cheng F Parl L Pierce YT Gao W Zheng (2005) ArticleTitleCytochrome P450 1B1 and catechol-O-methyltransferase genetic polymorphisms and breast cancer risk in Chinese women: results from the shanghai breast cancer study and a meta-analysis Cancer Epidemiol Biomarkers Prev 14 329–335 Occurrence Handle10.1158/1055-9965.EPI-04-0392 Occurrence Handle15734954 Occurrence Handle1:CAS:528:DC%2BD2MXhs1Ghs74%3D

    Article  PubMed  CAS  Google Scholar 

  38. SM Boyapati XO Shu YT Gao Q Dai H Yu JR Cheng F Jin W Zheng (2004) ArticleTitleCorrelation of blood sex steroid hormones with body size, body fat distribution, and other known risk factors for breast cancer in post-menopausal Chinese women Cancer Causes Control 15 305–311 Occurrence Handle10.1023/B:CACO.0000024256.48104.50 Occurrence Handle15090725

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Center for Health Services Research and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Gong Yang, Qiu-Yin Cai, Xiao-Ou Shu & Wei Zheng

  2. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

    Yu-Tang Gao & Jia-Rong Cheng

Authors
  1. Gong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Tang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiu-Yin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Ou Shu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia-Rong Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gong Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, G., Gao, YT., Cai, QY. et al. Modifying Effects of Sulfotransferase 1A1 Gene Polymorphism on the Association of Breast Cancer Risk with Body Mass Index or Endogenous Steroid Hormones. Breast Cancer Res Treat 94, 63–70 (2005). https://doi.org/10.1007/s10549-005-7280-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-005-7280-2

Key words

Search

Navigation