Genetic Variation in the HSD17B1 Gene and Risk of Prostate Cancer

Peter Kraft, Paul Pharoah, Stephen J. Chanock, Demetrius Albanes, Laurence N. Kolone, Richard B. Hayes, David Altshuler, Gerald Andriole, Christine Berg, Heiner Boeing, Noel P. Burtt, Bas Bueno-de-Mesquita, Eugenia E. Calle, Howard Cann, Federico Canzian, Yen Ching Chen, David E. Crawford, Alison M. Dunning, Heather S. Feigelson, Matthew L. FreedmanJohn M. Gaziano, Ed Giovannucci, Carlos Alberto Gonzalez, Christopher A. Haiman, Goran Hallmans, Brian E. Henderson, Joel N. Hirschhorn, David J. Hunter, Rudolf Kaaks, Timothy Key, Loic Le Marchand, Ma Jing, Kim Overvad, Domenico Palli, Malcolm C. Pike, Elio Riboli, Carmen Rodriguez, Wendy V. Setiawan, Meir J. Stampfer, Daniel O. Stram, Gilles Thomas, Michael J. Thun, Ruth Travis, Antonia Trichopoulou, Jarmo Virtamo, Sholom Wacholder

Research output: Contribution to journalArticle

Abstract

Steroid hormones are believed to play am important raie In prostate carcirtogenesis, but epidemioiogica! evidence unking prostate cancer and steroid hormone genes has been meoncSusive, in part dye to smai! sample sizes or incomplete characterization of genetic variation! at the locus of interest. Here we report ors the reswits of a comprehensive study of the association between HSD1781 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a iarge coHaborative study. HSD17B1 encodes 17β-hydroxysteraid dehydrogenase 1, art enzyme that converts dahydroepiandrosterane to the testosterone precursor ħ-androsteron6-3β,17β-d!Gl and converts estrarse to estradioa. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HS017S? by targeted resequeneing and dense genotyping; seiected hapiotype-tagging single nwcSeotide polymorphisms (htSMPsj that effiderstiy predict common variants in ILS, and European whites. Latinos, Japanese Americans, and Mative Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer eases and 9,367 stydy-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSMPs {inciudirsg the nonsyrsonymows coding SNP S312G) or htSMP hapfotypes were associated with risk of prostate cancer or tumor stage in the pooled myStiethnlc sample or In U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no sybgroyp-specific associations between these HSD17B1 htSMPs and prostate cancer. We foyrsd significant evidence of heterogeneity In associations between HSD17B1 hapiotypes and prostate cancer across ethnicity: one haplotype had a significant {p < 0.002} inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Mative Hawaiians, or whites. However, the smaiier numbers of Latinos and Japanese Americans in this study makes these subgroup analyses iess reliable. These results suggest that the germiine variants in HSD17B1 characterized by these htSMPs do not substantially influence the risk of prostate cancer in U.S. and European whites. Copyright:

Original languageEnglish (US)
Pages (from-to)603-613
Number of pages11
JournalPLoS genetics
Volume1
Issue number5
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Kraft, P., Pharoah, P., Chanock, S. J., Albanes, D., Kolone, L. N., Hayes, R. B., Altshuler, D., Andriole, G., Berg, C., Boeing, H., Burtt, N. P., Bueno-de-Mesquita, B., Calle, E. E., Cann, H., Canzian, F., Chen, Y. C., Crawford, D. E., Dunning, A. M., Feigelson, H. S., ... Wacholder, S. (2005). Genetic Variation in the HSD17B1 Gene and Risk of Prostate Cancer. PLoS genetics, 1(5), 603-613. https://doi.org/10.1371/journal.pgen.0010068