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A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer.

Publication ,  Journal Article
Lee, AW; Bomkamp, A; Bandera, EV; Jensen, A; Ramus, SJ; Goodman, MT; Rossing, MA; Modugno, F; Moysich, KB; Chang-Claude, J; Rudolph, A; Wu, AH ...
Published in: Int J Cancer
December 15, 2016

Menopausal estrogen-alone therapy (ET) is a well-established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome-wide association studies. The interplay among these loci, ET use and ovarian cancer risk has yet to be evaluated. We analyzed data from 1,414 serous cases, 337 endometrioid cases and 4,051 controls across 10 case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Conditional logistic regression was used to determine the association between the confirmed susceptibility variants and risk of serous and endometrioid ovarian cancer among ET users and non-users separately and to test for statistical interaction. A splicing variant in TERT, rs10069690, showed a statistically significant interaction with ET use for risk of serous ovarian cancer (pint  = 0.013). ET users carrying the T allele had a 51% increased risk of disease (OR = 1.51, 95% CI 1.19-1.91), which was stronger for long-term ET users of 10+ years (OR = 1.85, 95% CI 1.28-2.66, pint  = 0.034). Non-users showed essentially no association (OR = 1.08, 95% CI 0.96-1.21). Two additional genomic regions harboring rs7207826 (C allele) and rs56318008 (T allele) also had significant interactions with ET use for the endometrioid histotype (pint  = 0.021 and pint  = 0.037, respectively). Hence, three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow-up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

December 15, 2016

Volume

139

Issue

12

Start / End Page

2646 / 2654

Location

United States

Related Subject Headings

  • Telomerase
  • Risk
  • Population Surveillance
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Middle Aged
  • Menopause
  • Humans
 

Citation

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Lee, A. W., Bomkamp, A., Bandera, E. V., Jensen, A., Ramus, S. J., Goodman, M. T., … Ovarian Cancer Association Consortium, . (2016). A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer. Int J Cancer, 139(12), 2646–2654. https://doi.org/10.1002/ijc.30274
Lee, Alice W., Ashley Bomkamp, Elisa V. Bandera, Allan Jensen, Susan J. Ramus, Marc T. Goodman, Mary Anne Rossing, et al. “A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer.Int J Cancer 139, no. 12 (December 15, 2016): 2646–54. https://doi.org/10.1002/ijc.30274.
Lee AW, Bomkamp A, Bandera EV, Jensen A, Ramus SJ, Goodman MT, et al. A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer. Int J Cancer. 2016 Dec 15;139(12):2646–54.
Lee, Alice W., et al. “A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer.Int J Cancer, vol. 139, no. 12, Dec. 2016, pp. 2646–54. Pubmed, doi:10.1002/ijc.30274.
Lee AW, Bomkamp A, Bandera EV, Jensen A, Ramus SJ, Goodman MT, Rossing MA, Modugno F, Moysich KB, Chang-Claude J, Rudolph A, Gentry-Maharaj A, Terry KL, Gayther SA, Cramer DW, Doherty JA, Schildkraut JM, Kjaer SK, Ness RB, Menon U, Berchuck A, Mukherjee B, Roman L, Pharoah PD, Chenevix-Trench G, Olson S, Hogdall E, Wu AH, Pike MC, Stram DO, Pearce CL, Ovarian Cancer Association Consortium. A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer. Int J Cancer. 2016 Dec 15;139(12):2646–2654.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

December 15, 2016

Volume

139

Issue

12

Start / End Page

2646 / 2654

Location

United States

Related Subject Headings

  • Telomerase
  • Risk
  • Population Surveillance
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Middle Aged
  • Menopause
  • Humans