Skip to main content

Advertisement

SpringerLink
Log in

Association between the T27C polymorphism in the cytochrome P450 c17α (CYP17) gene and risk factors for breast cancer

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

Abstract

Mammographic density is associated with increased breast cancer risk and is influenced by sex hormones. A T27C polymorphism (alleles A1 and A2, respectively) in the 5′ promoter region of CYP17 may be associated with elevated sex hormone levels. In a cross-sectional study of 181 pre- and 173 postmenopausal women, we examined the relationship of this polymorphism with mammographic density and other risk factors for breast cancer. Subjects were recruited across five categories of density. Risk factor and dietary information, anthropometric measures, and blood samples were obtained. Sex hormone, lipid, growth factor levels, and CYP17 genotypes were determined. CYP17 genotype was not associated with mammographic density levels before or after adjusting for risk factors for breast cancer. In premenopausal women, the A2 allele was associated with higher levels of dehydroepiandrosterone sulfate, and in postmenopausal women, with higher levels of total estradiol and lower levels of follicle stimulating hormone. Among premenopausal women, interactions were observed between CYP17 genotype and endogenous insulin levels as well as dietary variables associated with mammographic density. Our findings suggest that the CYP17 A2 allele is associated with hormone levels, and interacts with insulin levels and diet to affect breast density levels and potentially 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

CYP17:

cytochrome p450 c17α

DHEA:

dehydroepiandrosterone

DHEAS:

dehydroepiandrosterone sulfate

FSH:

follicle stimulating hormone

GH:

growth hormone

HDL:

high density lipoprotein cholesterol

IGF-1:

insulin-like growth-factor-1

IGFBP-3:

insulin-like growth factor binding protein-3

LDL:

low density lipoproprotein cholesterol

SHBG:

sex hormone binding globulin

VLDL:

very low density lipoprotein cholesterol

WHR:

waist-to-hip ratio

References

  • InstitutionalAuthorNameThe Endogenous Hormonesand Breast Cancer Collaborative Group (2002) ArticleTitleEndogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies J Natl Cancer Inst 94 606–616

    Google Scholar 

  • H Olsson A Bladstrom (2002) ArticleTitleA cohort study of reproductive factors and family history of breast cancer in southern Sweden Breast Cancer Res Treat 76 203–209

    Google Scholar 

  • PH Lahmann L Lissner B Gullberg H Olsson G Berglund (2003) ArticleTitleA prospective study of adiposity and postmenopausal breast cancer risk: the Malmo Diet and Cancer Study Int J Cancer 103 246–252

    Google Scholar 

  • JE Rossouw GL Anderson RL Prentice AZ LaCroix C Kooperberg ML Stefanick RD Jackson SA Beresford BV Howard KC Johnson JM Kotchen J Ockene (2002) ArticleTitleRisks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial JAMA 288 321–333

    Google Scholar 

  • CM Vachon LH Kushi JR Cerhan CC Kuni TA Sellers (2000) ArticleTitleAssociation of diet and mammographic breast density in the Minnesota Breast Cancer Family Cohort Cancer Epidemiol Biomarkers Prev 9 151–160

    Google Scholar 

  • NF Boyd GA Lockwood J Byng DL Tritchler M Yaffe (1998) ArticleTitleMammographic densities and breast cancer risk Cancer Epidemiol Biomarkers Prev 7 1133–1144

    Google Scholar 

  • CM Vachon CC Kuni K Anderson VE Anderson TA Sellers (2000) ArticleTitleAssociation of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States) Cancer Causes Control 11 653–662

    Google Scholar 

  • NF Boyd GS Dite J Stone A Gunasekara DR English MRE McCredie GG Giles D Tritchler A Chiarelli MJ Yaffe JL Hopper (2002) ArticleTitleHeritability of mammographic density, a risk factor for breast cancer The New England J Med 347 886–894

    Google Scholar 

  • GA Greendale BA Reboussin A Sie R Singh LK Olson O Gatewood LW Bassett C Wasilauskas T Bush E Barrett-Connor (1999) ArticleTitleEffects of estrogen and estrogen-progestin on mammographic parenchymal density. Annals of Internal Medicine 130 IssueID4 262–269

    Google Scholar 

  • J Brisson B Brisson G Coté E Maunsell S Bérubé J Robert (2000) ArticleTitleTamoxifen and mammographic breast densities Cancer Epidemiol Biomarkers Prev 9 911–915

    Google Scholar 

  • WL Miller (1998) ArticleTitleEarly steps in androgen biosynthesis: from cholesterol to DHEA Baillieres Clin Endocrinol Metab 12 67–81

    Google Scholar 

  • HS Feigelson GA Coetzee LN Kolonel RK Ross BE Henderson (1997) ArticleTitleA polymorphism in the CYP17 gene increases the risk of breast cancer Cancer Res 57 1063–1065

    Google Scholar 

  • HS Feigelson LS Shames MC Pike GA Coetzee FZ Stanczyk BE Henderson (1998) ArticleTitlecytochrome p450c17 and gene (cyp17) polymorphism is associated with serum estrogen and progesterone concentrations Cancer Research 58 585–587

    Google Scholar 

  • CA Haiman SE Hankinson D Spiegelman GA Colditz WC Willett FE Speizer KT Kelsey DJ Hunter (1999) ArticleTitleThe relationship between a polymorphism in cyp17 with plasma hormone levels and breast cancer Cancer Research 59 1015–1020

    Google Scholar 

  • CA Haiman L Bernstein D Berg SA Ingles M Salane G Ursin (2002) ArticleTitleGenetic determinants of mammographic density. Breast Cancer Res 4 R5

    Google Scholar 

  • CA Haiman SE Hankinson VI De C Guillemette N Ishibe DJ Hunter C Byrne (2003) ArticleTitlePolymorphisms in steroid hormone pathway genes and mammographic density Breast Cancer Res Treat 77 27–36

    Google Scholar 

  • NF Boyd J Stone LJ Martin R Jong E Fishell M Yaffe G Hammond S Minkin (2002) ArticleTitleThe association of breast mitogens with mammographic densities. British J Cancer 87 IssueID8 876–882

    Google Scholar 

  • CC Hong HJ Thompson C Jiang GL Hammond D Tritchler M Yaffe NF Boyd (2003) ArticleTitleVal158Met Polymorphism in catechol-O-methyltransferase gene associated with risk factors for breast cancer Cancer Epidemiol Biomarkers Prev 12 838–847

    Google Scholar 

  • G Block FE Thompson AM Hartman FA Larkin KE Guire (1992) ArticleTitleComparison of two dietary questionnaires validated against multiple dietary records collected during a 1-year period J Am Diet Assoc 92 686–693

    Google Scholar 

  • G Block R Mandel E Gold (2004) ArticleTitleOn food frequency questionnaires: the contribution of open-ended questions and questions on ethnic foods Epidemiology 15 216–221

    Google Scholar 

  • MS Langley GL Hammond A Bardsley RA Sellwood DC Anderson (1985) ArticleTitleSerum steroid binding proteins and the bioavailability of estradiol in relation to breast diseases J Natl Cancer Inst 75 823–829

    Google Scholar 

  • National Heart LaBI: Manual of Laboratory Operations, Lipid Research Clinics Program – 1. Lipid and Lipoprotein Analysis. 2: 1982.

  • L Wang K Hirayasu M Ishizawa Y Kobayashi (1994) ArticleTitlePurification of genomic DNA from human whole blood by isopropanol-fractionation with concentrated Nal and SDS Nucleic Acids Res 22 1774–1775

    Google Scholar 

  • JW Byng NF Boyd E Fishell RA Jong MJ Yaffe (1994) ArticleTitleThe quantitative analysis of mammographic densities Phys Med Biol 39 1629–1638

    Google Scholar 

  • SAS Institute Inc: SAS/STAT User’s Guide, Version 6.4: 1989.

  • Katz MH: Multivariable Analysis: A Practical Guide for Clinicians, 1999.

  • KJ Helzlsouer H-Y Huang PT Strickland S Hoffman AJ Alberg GW Comstock DA Bell (1998) ArticleTitleAssociation between CYP17 polymorphisms and the development of breast cancer Cancer Epidemiol Biomarkers Prev 7 945–949

    Google Scholar 

  • LK Summers BA Fielding HA Bradshaw V Ilic C Beysen ML Clark NR Moore KN Frayn (2002) ArticleTitleSubstituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity Diabetologia 45 369–377

    Google Scholar 

  • S Paeratakul BM Popkin G Keyou LS Adair J Stevens (1998) ArticleTitleChanges in diet and physical activity affect the body mass index of Chinese adults Int J Obes Relat Metab Disord 22 424–431

    Google Scholar 

  • NE Sherwood RW Jeffery SA French PJ Hannan DM Murray (2000) ArticleTitlePredictors of weight gain in the Pound of Prevention study Int J Obes Relat Metab Disord 24 395–403

    Google Scholar 

  • Z Ye JM Parry (2002) ArticleTitleThe CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis Mutagenesis 17 119–126

    Google Scholar 

  • R Kaaks A Lukanova (2002) ArticleTitleEffects of weight control and physical activity in cancer prevention: role of endogenous hormone metabolism Ann N Y Acad Sci 963 268–281

    Google Scholar 

  • SA Kaye AR Folsom JT Soler RJ Prineas JD Potter (1991) ArticleTitleAssociations of body mass and fat distribution with sex hormone concentrations in postmenopausal women Int J Epidemiol 20 151–156

    Google Scholar 

  • S Teramukai T Rohan H Eguchi T Oda K Shinchi S Kono (2002) ArticleTitleAnthropometric and behavioral correlates of insulin-like growth factor I and insulin-like growth factor binding protein 3 in middle-aged Japanese men Am J Epidemiol 156 344–348

    Google Scholar 

  • A Lukanova S Soderberg P Stattin R Palmqvist E Lundin C Biessy S Rinaldi E Riboli G Hallmans R Kaaks (2002) ArticleTitleNonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF-binding protein-3 ratio with indices of adiposity and plasma insulin concentrations (Sweden) Cancer Causes Control 13 509–516

    Google Scholar 

  • H Yamamoto Y Kato (1993) ArticleTitleRelationship between plasma insulin-like growth factor I (IGF-I) levels and body mass index (BMI) in adults Endocr J 40 41–45

    Google Scholar 

  • DA Magoffin SR Weitsman (1993) ArticleTitleDifferentiation of ovarian theca-interstitial cells in vitro: regulation of 17 alpha-hydroxylase messenger ribonucleic acid expression by luteinizing hormone and insulin-like growth factor-I Endocrinology 132 1945–1951

    Google Scholar 

  • SB Kristiansen A Endoh PR Casson JE Buster PJ Hornsby (1997) ArticleTitleInduction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells Steroids 62 258–265

    Google Scholar 

  • JE Nestler DJ Jakubowicz (1996) ArticleTitleDecreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome N Engl J Med 335 617–623

    Google Scholar 

  • WL Miller RJ Auchus DH Geller (1997) ArticleTitleThe regulation of 17,20 lyase activity Steroids 62 133–142

    Google Scholar 

  • SR Plymate LA Matej RE Jones KE Friedl (1988) ArticleTitleInhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin J Clin Endocrinol Metab 67 460–464

    Google Scholar 

  • PG Clauson K Brismar K Hall R Linnarsson V Grill (1998) ArticleTitleInsulin-like growth factor-I and insulin-like growth factor binding protein-1 in a representative population of type 2 diabetic patients in Sweden Scand J Clin Lab Invest 58 353–360

    Google Scholar 

  • PR Casson LC Faquin FB Stentz AB Straughn RN Andersen GE Abraham JE Buster (1995) ArticleTitleReplacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in postmenopausal women Fertil Steril 63 1027–1031

    Google Scholar 

  • YJ Janssen F Helmerhorst M Frolich F Roelfsema (2000) ArticleTitleA switch from oral (2 mg/day) to transdermal (50 microg/day) 17beta-estradiol therapy increases serum insulin-like growth factor-I levels in recombinant human growth hormone (GH)-substituted women with GH deficiency J Clin Endocrinol Metab 85 464–467

    Google Scholar 

  • A Cano C Castelo-branco JJ Tarin (1999) ArticleTitleEffect of menopause and different combined estradiol-progestin regimens on basal and growth hormone-releasing hormone-stimulated serum growth hormone, insulin-like growth factor-1, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3 levels. Fertil Steril 71 IssueID2 261–267

    Google Scholar 

  • TJ Key (1999) ArticleTitleSerum oestradiol and breast cancer risk Endocr Relat Cancer 6 175–180

    Google Scholar 

  • IT Gram G Ursin DV Spicer MC Pike (2001) ArticleTitleReversal of gonadotropin-releasing hormone agonist induced reductions in mammographic densities on stopping treatment Cancer Epidemiol Biomarkers Prev 10 1117–1120

    Google Scholar 

  • SE Hankinson WC Willet GA Colditz DJ Hunter DS Michaud B Deroo B Rosner FE Speizer M Pollak (1998) ArticleTitleCirculating concentrations of insulin-like growth factor-I and risk of breast cancer Lancet 351 1393–1396

    Google Scholar 

  • C Byrne GA Colditz WC Willet FE Speizer M Pollak SE Hankinson (2000) ArticleTitlePlasma insulin-like growth factor (IGF) I, IGF-binding Protein 3, and mammographic density Cancer Research 60 3744–3748

    Google Scholar 

  • ME Del Giudice IG Fantus S Ezzat G McKeown-Eyssen D Page PJ Goodwin (1998) ArticleTitleInsulin and related factors in premenopausal breast cancer risk Breast Cancer Res Treat 47 111–120

    Google Scholar 

  • PF Bruning JMG Bonfrèr PAH Noord Particlevan AAM Hart M Jong-Bakker Particlede WJ Nooijen (1992) ArticleTitleInsulin resistance and breast-cancer risk Int J Cancer 52 511–516

    Google Scholar 

  • K Mitrunen N Jourenkova V Kataja M Eskelinen VM Kosma S Benhamou H Vainio M Uusitupa A Hirvonen (2000) ArticleTitleSteroid metabolism gene CYP17 polymorphism and the development of breast cancer Cancer Epidemiol Biomarkers Prev 9 1343–1348

    Google Scholar 

  • MT Goodman K McDuffie C Guo K Terada TA Donlon (2001) ArticleTitleCYP17 genotype and ovarian cancer: a null case–control study Cancer Epidemiol Biomarkers Prev 10 563–564

    Google Scholar 

  • CB Ambrosone KB Moysich H Furberg JL Freudenheim ED Bowman S Ahmed S Graham JE Vena PG Shields (2003) ArticleTitleCYP17 genetic polymorphism, breast cancer, and breast cancer risk factors Breast Cancer Res 5 R45–R51

    Google Scholar 

  • HS Feigelson R McKean-Cowdin MC Pike GA Coetzee LN Kolonel AMY Nomura LL Marchand BE Henderson (1999) ArticleTitleCytochrome p450c17 and gene (cyp17) polymorphism predicts use of hormone replacement therapy Cancer Research 59 3908–3910

    Google Scholar 

  • CA Haiman SE Hankinson GAz Coldit DJ Hunter I Vivo ParticleDe (2001) ArticleTitleA polymorphism in cyp17 and endometrial cancer risk Cancer Research 61 3955–3960

    Google Scholar 

  • M Garcia-Closas J Herbstman M Schiffman A Glass JF Dorgan (2002) ArticleTitleRelationship between serum hormone concentrations, reproductive history, alcohol consumption and genetic polymorphisms in pre-menopausal women Int J Cancer 102 172–178

    Google Scholar 

  • SS Tworoger J Chubak EJ Aiello CM Ulrich C Atkinson JD Potter Y Yasui PL Stapleton JW Lampe FM Farin FZ Stanczyk A McTiernan (2004) ArticleTitleAssociation of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women Cancer Epidemiol Biomarkers Prev 13 94–101

    Google Scholar 

  • P Muti M Trevisan A Micheli V Krogh G Bolelli R Sciajno F Berrino (1996) ArticleTitleReliability of serum hormones in premenopausal and postmenopausal women over a one-year period Cancer Epidemiol Biomarkers Prev 5 917–922

    Google Scholar 

  • DS Michaud JE Manson D Spiegelman RL Barbieri D Sepkovic HL Bradlow SE Hankinson (1999) ArticleTitleReproducibility of plasma and urinary sex hormone levels in premenopausal women over a one-year period Cancer Epidemiol Biomarkers Prev 8 1059–1064

    Google Scholar 

  • AD Genazzani M Stomati C Strucchi S Puccetti S Luisi AR Genazzani (2001) ArticleTitleOral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women Fertil Steril 76 241–248

    Google Scholar 

  • D Goodman-Gruen E Barrett-Connor (1997) ArticleTitleEpidemiology of insulin-like growth factor-I in elderly men and women. The Rancho Bernardo Study Am J Epidemiol 145 970–976

    Google Scholar 

  • A Weston C-F Pan IJ Bleiweiss HB Ksieski N Roy N Maloney MS Wolff (1998) ArticleTitleCYP17 genotype and breast cancer risk. Cancer Epidemiol Biomarkers Prev 7 941–944

    Google Scholar 

  • AH Wu A Seow K Arakawa BD Van Den HP Lee MC Yu (2003) ArticleTitleHSD17B1 and CYP17 polymorphisms and breast cancer risk among Chinese women in Singapore Int J Cancer 104 450–457

    Google Scholar 

  • PJ Goodwin M Ennis KI Pritchard ME Trudeau J Koo Y Madarnas W Hartwick B Hoffman N Hood (2002) ArticleTitleFasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study J Clin Oncol 20 42–51

    Google Scholar 

  • CN Tymchuk SB Tessler WJ Aronson RJ Barnard (1998) ArticleTitleEffects of diet and exercise on insulin, sex hormone-binding globulin, and prostate-specific antigen Nutr Cancer 31 127–131

    Google Scholar 

  • JE Nestler DJ Jakubowicz (1997) ArticleTitleLean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens J Clin Endocrinol Metab 82 4075–4079

    Google Scholar 

  • A Ivandic I Prpic-Krizevac M Sucic M Juric (1998) ArticleTitleHyperinsulinemia and sex hormones in healthy premenopausal women: relative contribution of obesity, obesity type, and duration of obesity Metabolism 47 13–19

    Google Scholar 

  • SA Smith-Warner D Spiegelman SS Yaun PA Brandt Particlevan den AR Goldbohm S Graham L Holmberg G Howe JR Marshall AB Miller JD Potter FE Speizer WC Willett A Wolk DJ Hunter (1998) ArticleTitleAlcohol and breast cancer in women: A pooled analysis of cohort studies JAMA 279 535–540

    Google Scholar 

  • JA Knight LJ Martin CV Greenberg GA Lockwood JW Byng MJ Yaffe DL Tritchler NF Boyd (1999) ArticleTitleMacronutrient intake and change in mammographic density at menopause: results from a randomized trial Cancer Epidemiol Biomarkers Prev 8 123–128

    Google Scholar 

  • J Brisson R Verreault A Morrison S Tennina F Meyer (1989) ArticleTitleDiet, mammographic features of breast tissue, and breast cancer risk Am J Epidemiol 130 14–24

    Google Scholar 

  • E Velie M Kulldorff C Schairer G Block D Albanes A Schatzkin (2000) ArticleTitleDietary fat, fat subtypes, and breast cancer in postmenopausal women: a prospective cohort study J Natl Cancer Inst 92 833–839

    Google Scholar 

  • ME Reichman JT Judd C Longcope A Schatzkin BA Clevidence PP Nair WS Campbell PR Taylor (1993) ArticleTitleEffects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women J Natl Cancer Inst 85 722–727

    Google Scholar 

  • MD Holmes D Spiegelman WC Willett JE Manson DJ Hunter RL Barbieri GA Colditz SE Hankinson (2000) ArticleTitleDietary fat intake and endogenous sex steroid hormone levels in postmenopausal women J Clin Oncol 18 3668–3676

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Epidemiology and Statistics, Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada

    Chi-chen Hong, David Tritchler & Norman F. Boyd

  2. Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO

    Henry J. Thompson

  3. The Hormel Institute, University of Minnesota, Northeast Austin, MN, USA

    Cheng Jiang

  4. B.C. Research Institute for Children’s and Women’s Health, Vancouver, British Columbia

    Geoffrey L. Hammond

  5. Medical Imaging Research Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada

    Martin Yaffe

Authors
  1. Chi-chen Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry J. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheng Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Geoffrey L. Hammond
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Tritchler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martin Yaffe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Norman F. Boyd
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norman F. Boyd.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hong, Cc., Thompson, H.J., Jiang, C. et al. Association between the T27C polymorphism in the cytochrome P450 c17α (CYP17) gene and risk factors for breast cancer. Breast Cancer Res Treat 88, 217–230 (2004). https://doi.org/10.1007/s10549-004-0780-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-004-0780-7

Keywords

Search

Navigation