Lee, AW;
Bomkamp, A;
Bandera, EV;
Jensen, A;
Ramus, SJ;
Goodman, MT;
Rossing, MA;
... Ovarian Cancer Association Consortium; + view all
(2016)
A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer.
International Journal of Cancer
, 139
(12)
pp. 2646-2654.
10.1002/ijc.30274.
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Gentry-Maharaj_Lee et al_A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer_Int J Can_2016.pdf Download (500kB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ijc.30274 |
| Publisher version: | http://dx.doi.org/10.1002/ijc.30274 |
| Language: | English |
| Additional information: | This is the peer reviewed version of the following article: Lee, AW; Bomkamp, A; Bandera, EV; Jensen, A; Ramus, SJ; Goodman, MT; Rossing, MA; (2016) A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer. International Journal of Cancer, 139 (12) pp. 2646-2654, which has been published in final form at: http://dx.doi.org/10.1002/ijc.30274. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms). |
| Keywords: | SNPs, estrogen, gene-environment interactions, hormone therapy, ovarian cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1506390 |
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