Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies.

Abstract

The 17beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) encodes 17HSD1, which catalyzes the final step of estradiol biosynthesis. Despite the important role of HSD17B1 in hormone metabolism, few epidemiologic studies of HSD17B1 and breast cancer have been conducted. This study includes 5,370 breast cancer cases and 7,480 matched controls from five large cohorts in the Breast and Prostate Cancer Cohort Consortium. We characterized variation in HSD17B1 by resequencing and dense genotyping a multiethnic sample and identified haplotype-tagging single nucleotide polymorphisms (htSNP) that capture common variation within a 33.3-kb region around HSD17B1. Four htSNPs, including the previously studied SNP rs605059 (S312G), were genotyped to tag five common haplotypes in all cases and controls. Conditional logistic regression was used to estimate odds ratios (OR) for disease. We found no evidence of association between common HSD17B1 haplotypes or htSNPs and overall risk of breast cancer. The OR for each haplotype relative to the most common haplotype ranged from 0.98 to 1.07 (omnibus test for association: X2 = 3.77, P = 0.58, 5 degrees of freedom). When cases were subdivided by estrogen receptor (ER) status, two common haplotypes were associated with ER-negative tumors (test for trend, Ps = 0.0009 and 0.0076; n = 353 cases). HSD17B1 variants that are common in Caucasians are not associated with overall risk of breast cancer; however, there was an association among the subset of ER-negative tumors. Although the probability that these ER-negative findings are false-positive results is high, these findings were consistent across each cohort examined and warrant further study.

• Authors: Heather Spencer Feigelson, David G Cox, Howard M Cann, Sholom Wacholder, Rudolf Kaaks, Brian E Henderson, Demetrius Albanes, David Altshuler, Goran Berglund, Franco Berrino, Sheila Bingham, Julie E Buring, Noel P Burtt, Eugenia E Calle, Stephen J Chanock, Francoise Clavel-Chapelon, Graham Colditz, W Ryan Diver, Matthew L Freedman, Christopher A Haiman, Susan E Hankinson, Richard B Hayes, Joel N Hirschhorn, David Hunter, Laurence N Kolonel, Peter Kraft, Loic LeMarchand, Jakob Linseisen, William Modi, Carmen Navarro, Petra H Peeters, Malcolm C Pike, Elio Riboli, V Wendy Setiawan, Daniel O Stram, Gilles Thomas, Michael J Thun, Anne Tjonneland, Dimitrios Trichopoulos
• Journal: Cancer research (Cancer Res) Vol. 66 Issue 4 Pg. 2468-75 (Feb 15 2006) ISSN: 0008-5472 [Print] United States
• PMID: 16489054 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• 17-Hydroxysteroid Dehydrogenases

Topics

• 17-Hydroxysteroid Dehydrogenases (genetics)
• Aged
• Breast Neoplasms (enzymology, genetics)
• Case-Control Studies
• Cohort Studies
• Female
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Middle Aged
• Prospective Studies