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

Feigelson, HS; Cox, DG; Cann, HM; Wacholder, S; Kaaks, R; Henderson, BE; Albanes, D; Altshuler, D; Berglund, Göran LU and Berrino, F, et al. (2006) In Cancer Research 66(4). p.2468-2475
Abstract
The 17 beta-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... (More)
The 17 beta-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: X-2 = 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. (Less)
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Contribution to journal
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published
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Cancer Research
volume
66
issue
4
pages
2468 - 2475
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:16489054
  • wos:000235387200074
  • scopus:33644551527
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-05-3574
language
English
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yes
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6687a936-68ea-4eae-8247-267764a7eea3 (old id 417556)
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http://cancerres.aacrjournals.org/cgi/content/abstract/66/4/2468
date added to LUP
2007-10-02 19:30:27
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2019-09-17 03:12:42
@article{6687a936-68ea-4eae-8247-267764a7eea3,
  abstract     = {The 17 beta-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: X-2 = 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.},
  author       = {Feigelson, HS and Cox, DG and Cann, HM and Wacholder, S and Kaaks, R and Henderson, BE and Albanes, D and Altshuler, D and Berglund, Göran and Berrino, F and Bingham, S and Buring, JE and Burtt, NP and Calle, EE and Chanock, SJ and Clavel-Chapelon, F and Colditz, G and Diver, WR and Freedman, ML and Haiman, CA and Hankinson, SE and Hayes, RB and Hirschhorn, JN and Hunter, D and Kolonel, LN and Kraft, P and LeMarchand, L and Linseisen, J and Modi, W and Navarro, C and Peeters, PH and Pike, MC and Riboli, E and Setiawan, VW and Stram, DO and Thomas, G and Thun, MJ and Tjonneland, A and Trichopoulos, D},
  issn         = {1538-7445},
  language     = {eng},
  number       = {4},
  pages        = {2468--2475},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Haplotype analysis of the HSD17B1 gene and risk of breast cancer: A comprehensive approach to multicenter analyses of prospective cohort studies},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-05-3574},
  volume       = {66},
  year         = {2006},
}