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Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

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  • Shalaka S Hampras
  • Lara E Sucheston-Campbell
  • Rikki Cannioto
  • Jenny Chang-Claude
  • Francesmary Modugno
  • Thilo Dörk
  • Peter Hillemanns
  • Leah Preus
  • Keith L Knutson
  • Paul K Wallace
  • Chi-Chen Hong
  • Grace Friel
  • Warren Davis
  • Mary Nesline
  • Celeste L Pearce
  • Linda E Kelemen
  • Marc T Goodman
  • Elisa V Bandera
  • Kathryn L Terry
  • Nils Schoof
  • Kevin H Eng
  • Alyssa Clay
  • Prashant K Singh
  • Janine M Joseph
  • Katja K H Aben
  • Hoda Anton-Culver
  • Natalia Antonenkova
  • Helen Baker
  • Yukie Bean
  • Matthias W Beckmann
  • Maria Bisogna
  • Line Bjorge
  • Natalia Bogdanova
  • Louise A Brinton
  • Angela Brooks-Wilson
  • Fiona Bruinsma
  • Ralf Butzow
  • Ian G Campbell
  • Karen Carty
  • Linda S Cook
  • Daniel W Cramer
  • Cezary Cybulski
  • Agnieszka Dansonka-Mieszkowska
  • Joe Dennis
  • Evelyn Despierre
  • Ed Dicks
  • Jennifer A Doherty
  • Andreas du Bois
  • Matthias Dürst
  • Doug Easton
  • Diana Eccles
  • Robert P Edwards
  • Arif B Ekici
  • Peter A Fasching
  • Brooke L Fridley
  • Yu-Tang Gao
  • Aleksandra Gentry-Maharaj
  • Graham G Giles
  • Rosalind Glasspool
  • Jacek Gronwald
  • Patricia Harrington
  • Philipp Harter
  • Hanis Nazihah Hasmad
  • Alexander Hein
  • Florian Heitz
  • Michelle A T Hildebrandt
  • Claus Hogdall
  • Estrid Vilma Solyom Høgdall
  • Satoyo Hosono
  • Edwin S Iversen
  • Anna Jakubowska
  • Allan Jensen
  • Bu-Tian Ji
  • Beth Y Karlan
  • Melissa Kellar
  • Joseph L Kelley
  • Lambertus A Kiemeney
  • Rüdiger Klapdor
  • Nonna Kolomeyevskaya
  • Camilla Krakstad
  • Susanne K Kjaer
  • Bridget Kruszka
  • Jolanta Kupryjanczyk
  • Diether Lambrechts
  • Sandrina Lambrechts
  • Nhu D Le
  • Alice W Lee
  • Shashikant Lele
  • Arto Leminen
  • Jenny Lester
  • Douglas A Levine
  • Dong Liang
  • Jolanta Lissowska
  • Song Liu
  • Karen Lu
  • Jan Lubinski
  • Lene Lundvall
  • Leon F A G Massuger
  • Keitaro Matsuo
  • Valeria McGuire
  • John R McLaughlin
  • Ian McNeish
  • Usha Menon
  • Joanna Moes-Sosnowska
  • Steven A Narod
  • Lotte Nedergaard
  • Heli Nevanlinna
  • Stefan Nickels
  • Sara H Olson
  • Irene Orlow
  • Rachel Palmieri Weber
  • James Paul
  • Tanja Pejovic
  • Liisa M Pelttari
  • Barbara Perkins
  • Jenny Permuth-Wey
  • Malcolm C Pike
  • Joanna Plisiecka-Halasa
  • Elizabeth M Poole
  • Harvey A Risch
  • Mary Anne Rossing
  • Joseph H Rothstein
  • Anja Rudolph
  • Ingo B Runnebaum
  • Iwona K Rzepecka
  • Helga B Salvesen
  • Eva Schernhammer
  • Kristina Schmitt
  • Ira Schwaab
  • Xiao-Ou Shu
  • Yurii B Shvetsov
  • Nadeem Siddiqui
  • Weiva Sieh
  • Honglin Song
  • Melissa C Southey
  • Ingvild L Tangen
  • Soo-Hwang Teo
  • Pamela J Thompson
  • Agnieszka Timorek
  • Ya-Yu Tsai
  • Shelley S Tworoger
  • Jonathan Tyrer
  • Anna M van Altena
  • Ignace Vergote
  • Robert A Vierkant
  • Christine Walsh
  • Shan Wang-Gohrke
  • Nicolas Wentzensen
  • Alice S Whittemore
  • Kristine G Wicklund
  • Lynne R Wilkens
  • Anna H Wu
  • Xifeng Wu
  • Yin-Ling Woo
  • Hannah Yang
  • Wei Zheng
  • Argyrios Ziogas
  • Simon A Gayther
  • Susan J Ramus
  • Thomas A Sellers
  • Joellen M Schildkraut
  • Catherine M Phelan
  • Andrew Berchuck
  • Georgia Chenevix-Trench
  • Julie M Cunningham
  • Paul P Pharoah
  • Roberta B Ness
  • Kunle Odunsi
  • Ellen L Goode
  • Kirsten B Moysich
Vis graf over relationer

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.

METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.

RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).

CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

OriginalsprogEngelsk
TidsskriftOncotarget
Vol/bind7
Udgave nummer43
Sider (fra-til)69097-69110
ISSN1949-2553
DOI
StatusUdgivet - 2016

ID: 49500119