A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer
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A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer. / Lee, Alice W; Bomkamp, Ashley; Bandera, Elisa V; Jensen, Allan; Ramus, Susan J; Goodman, Marc T; Rossing, Mary Anne; Modugno, Francesmary; Moysich, Kirsten B; Chang-Claude, Jenny; Gentry-Maharaj, Aleksandra; Terry, Kathryn L; Gayther, Simon A; Cramer, Daniel W; Doherty, Jennifer A; Schildkraut, Joellen M; Kjaer, Susanne K; Ness, Roberta B; Menon, Usha; Berchuck, Andrew; Mukherjee, Bhramar; Roman, Lynda; Pharoah, Paul D; Chenevix-Trench, Georgia; Olson, Sara; Hogdall, Estrid; Wu, Anna H; Pike, Malcolm C; Stram, Daniel O; Pearce, Celeste Leigh; Ovarian Cancer Association Consortium.
in: INT J CANCER, Jahrgang 139, Nr. 12, 15.12.2016, S. 2646–2654.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer
AU - Lee, Alice W
AU - Bomkamp, Ashley
AU - Bandera, Elisa V
AU - Jensen, Allan
AU - Ramus, Susan J
AU - Goodman, Marc T
AU - Rossing, Mary Anne
AU - Modugno, Francesmary
AU - Moysich, Kirsten B
AU - Chang-Claude, Jenny
AU - Gentry-Maharaj, Aleksandra
AU - Terry, Kathryn L
AU - Gayther, Simon A
AU - Cramer, Daniel W
AU - Doherty, Jennifer A
AU - Schildkraut, Joellen M
AU - Kjaer, Susanne K
AU - Ness, Roberta B
AU - Menon, Usha
AU - Berchuck, Andrew
AU - Mukherjee, Bhramar
AU - Roman, Lynda
AU - Pharoah, Paul D
AU - Chenevix-Trench, Georgia
AU - Olson, Sara
AU - Hogdall, Estrid
AU - Wu, Anna H
AU - Pike, Malcolm C
AU - Stram, Daniel O
AU - Pearce, Celeste Leigh
AU - Ovarian Cancer Association Consortium
N1 - © 2016 UICC.
PY - 2016/12/15
Y1 - 2016/12/15
N2 - 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, a total of 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. This article is protected by copyright. All rights reserved.
AB - 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, a total of 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. This article is protected by copyright. All rights reserved.
U2 - 10.1002/ijc.30274
DO - 10.1002/ijc.30274
M3 - SCORING: Journal article
C2 - 27420401
VL - 139
SP - 2646
EP - 2654
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 12
ER -
