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

Eva Lundin, Isaac Wirgin, Annekatrin Lukanova, Yelena Afanasyeva, Vittorio Krogh, Tomas Axelsson, Kari Hemminki, Tess V. Clendenen, Alan A. Arslan, Nina Ohlson, Sabina Sieri, Nirmal Roy, Karen L. Koenig, Annika Idahl, Franco Berrino, Paolo Toniolo, Göran Hallmans, Asta Försti, Paola Muti, Per Lenner & 2 others Roy E. Shore, Anne Zeleniuch-Jacquotte

Research output: Contribution to journalArticle

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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, ptrend=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, ptrend=0.06). PGR rs1042838 was also marginally associated with risk (ORper allele=1.25, 95% CI=0.96-1.61, ptrend=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.

Original languageEnglish
Pages (from-to)445-452
Number of pages8
JournalCancer Epidemiology
Volume36
Issue number5
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Gonadal Steroid Hormones
Endometrial Neoplasms
Alleles
Genes
Case-Control Studies
Estradiol
Aromatase
Estrone
Blood Donors
Progesterone
Estrogens
Cross-Sectional Studies
Hormones
Breast Neoplasms

Keywords

  • Endometrial cancer
  • Estrogen
  • Progesterone receptor
  • Sex hormone-binding globulin
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Epidemiology

Cite this

Lundin, E., Wirgin, I., Lukanova, A., Afanasyeva, Y., Krogh, V., Axelsson, T., ... Zeleniuch-Jacquotte, A. (2012). Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer. Cancer Epidemiology, 36(5), 445-452. https://doi.org/10.1016/j.canep.2012.04.006

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; Clendenen, Tess V.; Arslan, Alan A.; Ohlson, Nina; Sieri, Sabina; Roy, Nirmal; Koenig, Karen L.; Idahl, Annika; Berrino, Franco; Toniolo, Paolo; Hallmans, Göran; Försti, Asta; Muti, Paola; Lenner, Per; Shore, Roy E.; Zeleniuch-Jacquotte, Anne.

In: Cancer Epidemiology, Vol. 36, No. 5, 10.2012, p. 445-452.

Research output: Contribution to journalArticle

Lundin, E, Wirgin, I, Lukanova, A, Afanasyeva, Y, Krogh, V, Axelsson, T, Hemminki, K, Clendenen, TV, Arslan, AA, Ohlson, N, Sieri, S, Roy, N, Koenig, KL, Idahl, A, Berrino, F, Toniolo, P, Hallmans, G, Försti, A, Muti, P, Lenner, P, Shore, RE & Zeleniuch-Jacquotte, A 2012, 'Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer', Cancer Epidemiology, vol. 36, no. 5, pp. 445-452. https://doi.org/10.1016/j.canep.2012.04.006
Lundin, Eva ; Wirgin, Isaac ; Lukanova, Annekatrin ; Afanasyeva, Yelena ; Krogh, Vittorio ; Axelsson, Tomas ; Hemminki, Kari ; Clendenen, Tess V. ; Arslan, Alan A. ; Ohlson, Nina ; Sieri, Sabina ; Roy, Nirmal ; Koenig, Karen L. ; Idahl, Annika ; Berrino, Franco ; Toniolo, Paolo ; Hallmans, Göran ; Försti, Asta ; Muti, Paola ; Lenner, Per ; Shore, Roy E. ; Zeleniuch-Jacquotte, Anne. / Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer. In: Cancer Epidemiology. 2012 ; Vol. 36, No. 5. pp. 445-452.
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AU - Wirgin, Isaac

AU - Lukanova, Annekatrin

AU - Afanasyeva, Yelena

AU - Krogh, Vittorio

AU - Axelsson, Tomas

AU - Hemminki, Kari

AU - Clendenen, Tess V.

AU - Arslan, Alan A.

AU - Ohlson, Nina

AU - Sieri, Sabina

AU - Roy, Nirmal

AU - Koenig, Karen L.

AU - Idahl, Annika

AU - Berrino, Franco

AU - Toniolo, Paolo

AU - Hallmans, Göran

AU - Försti, Asta

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N2 - 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, ptrend=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, ptrend=0.06). PGR rs1042838 was also marginally associated with risk (ORper allele=1.25, 95% CI=0.96-1.61, ptrend=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.

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