Forskning ved Københavns Universitet - Københavns Universitet


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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Alice W Lee
  • Ashley Bomkamp
  • Elisa V Bandera
  • Allan Jensen
  • Susan J Ramus
  • Marc T Goodman
  • Mary Anne Rossing
  • Francesmary Modugno
  • Kirsten B Moysich
  • Jenny Chang-Claude
  • Anja Rudolph
  • Aleksandra Gentry-Maharaj
  • Kathryn L Terry
  • Simon A Gayther
  • Daniel W Cramer
  • Jennifer A Doherty
  • Joellen M Schildkraut
  • Kjær, Susanne Krüger
  • Roberta B Ness
  • Usha Menon
  • Andrew Berchuck
  • Bhramar Mukherjee
  • Lynda Roman
  • Paul D Pharoah
  • Georgia Chenevix-Trench
  • Sara Olson
  • Høgdall, Estrid Vilma Solyom
  • Anna H Wu
  • Malcolm C Pike
  • Daniel O Stram
  • Celeste Leigh Pearce
  • Ovarian Cancer Association Consortium

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.

TidsskriftInternational Journal of Cancer
Udgave nummer12
Sider (fra-til)2646-2654
Antal sider9
StatusUdgivet - 15 dec. 2016

ID: 167585729