TY - JOUR
T1 - Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer
AU - on behalf of the Australian Ovarian Cancer Study Group
AU - Hampras, Shalaka S.
AU - Sucheston-Campbell, Lara E.
AU - Cannioto, Rikki
AU - Chang-Claude, Jenny
AU - Modugno, Francesmary
AU - Dörk, Thilo
AU - Hillemanns, Peter
AU - Preus, Leah
AU - Knutson, Keith L.
AU - Wallace, Paul K.
AU - Hong, Chi Chen
AU - Friel, Grace
AU - Davis, Warren
AU - Nesline, Mary
AU - Pearce, Celeste L.
AU - Kelemen, Linda E.
AU - Goodman, Marc T.
AU - Bandera, Elisa V.
AU - Terry, Kathryn L.
AU - Schoof, Nils
AU - Eng, Kevin H.
AU - Clay, Alyssa
AU - Singh, Prashant K.
AU - Joseph, Janine M.
AU - Aben, Katja K.H.
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia
AU - Baker, Helen
AU - Bean, Yukie
AU - Beckmann, Matthias W.
AU - Bisogna, Maria
AU - Bjorge, Line
AU - Bogdanova, Natalia
AU - Brinton, Louise A.
AU - Brooks-Wilson, Angela
AU - Bruinsma, Fiona
AU - Butzow, Ralf
AU - Campbell, Ian G.
AU - Carty, Karen
AU - Cook, Linda S.
AU - Cramer, Daniel W.
AU - Cybulski, Cezary
AU - Dansonka-Mieszkowska, Agnieszka
AU - Dennis, Joe
AU - Despierre, Evelyn
AU - Dicks, Ed
AU - Doherty, Jennifer A.
AU - du Bois, Andreas
AU - Liu, Song
AU - Moysich, Kirsten B.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Genetic variation
KW - Immunosuppression
KW - Ovarian cancer
KW - TGFBR2
UR - https://www.scopus.com/pages/publications/84994344826
U2 - 10.18632/oncotarget.10215
DO - 10.18632/oncotarget.10215
M3 - Article
C2 - 27533245
AN - SCOPUS:84994344826
SN - 1949-2553
VL - 7
SP - 69097
EP - 69110
JO - Oncotarget
JF - Oncotarget
IS - 43
ER -