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Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer

Lundin, Eva; Wirgin, Isaac; Lukanova, Annekatrin; Afanasyeva, Yelena; Krogh, Vittorio; Axelsson, Tomas; Hemminki, Kari LU ; Clendenen, Tess V.; Arslan, Alan A. and Ohlson, Nina, et al. (2012) In Cancer Epidemiology 36(5). p.445-452
Abstract
Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested... (More)
Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (ORper allele = 1.22, 95% CI = 1.01-1.47, p(trend) = 0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (ORper allele = 1.20, 95% CI = 0.99-1.45, p(trend) = 0.06). PGR rs1042838 was also marginally associated with risk (ORper allele = 1.25, 95% CI = 0.96-1.61, p(trend) = 0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer. (C) 2012 Elsevier Ltd. All rights reserved. (Less)
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keywords
Endometrial cancer, Estrogen, Sex hormone-binding globulin, Progesterone, receptor, Single nucleotide polymorphism
in
Cancer Epidemiology
volume
36
issue
5
pages
445 - 452
publisher
Elsevier
external identifiers
  • wos:000309818500017
  • scopus:84866238503
ISSN
1877-7821
DOI
10.1016/j.canep.2012.04.006
language
English
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yes
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29983b0d-6cfe-481a-ac7f-7ef60f3e32a9 (old id 3287596)
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2013-01-07 09:43:23
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2017-08-06 03:09:24
@article{29983b0d-6cfe-481a-ac7f-7ef60f3e32a9,
  abstract     = {Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (ORper allele = 1.22, 95% CI = 1.01-1.47, p(trend) = 0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (ORper allele = 1.20, 95% CI = 0.99-1.45, p(trend) = 0.06). PGR rs1042838 was also marginally associated with risk (ORper allele = 1.25, 95% CI = 0.96-1.61, p(trend) = 0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer. (C) 2012 Elsevier Ltd. All rights reserved.},
  author       = {Lundin, Eva and Wirgin, Isaac and Lukanova, Annekatrin and Afanasyeva, Yelena and Krogh, Vittorio and Axelsson, Tomas and Hemminki, Kari and Clendenen, Tess V. and Arslan, Alan A. and Ohlson, Nina and Sieri, Sabina and Roy, Nirmal and Koenig, Karen L. and Idahl, Annika and Berrino, Franco and Toniolo, Paolo and Hallmans, Goran and Försti, Asta and Muti, Paola and Lenner, Per and Shore, Roy E. and Zeleniuch-Jacquotte, Anne},
  issn         = {1877-7821},
  keyword      = {Endometrial cancer,Estrogen,Sex hormone-binding globulin,Progesterone,receptor,Single nucleotide polymorphism},
  language     = {eng},
  number       = {5},
  pages        = {445--452},
  publisher    = {Elsevier},
  series       = {Cancer Epidemiology},
  title        = {Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer},
  url          = {http://dx.doi.org/10.1016/j.canep.2012.04.006},
  volume       = {36},
  year         = {2012},
}