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

On behalf of the Australian Ovarian Cancer Study Group

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)69097-69110
Number of pages14
JournalOncotarget
Volume7
Issue number43
DOIs
StatePublished - 2016
Externally publishedYes

Fingerprint

Immunosuppressive Agents
Ovarian Neoplasms
Regulatory T-Lymphocytes
Genes
Single Nucleotide Polymorphism
Galectin 1
Lymphokines
Interleukin-12
Antigen-Antibody Complex
Immunosuppression
Messenger RNA
Ovarian epithelial cancer
Population
Neoplasms

Keywords

  • Biomarkers
  • Genetic variation
  • Immunosuppression
  • Ovarian cancer
  • TGFBR2

ASJC Scopus subject areas

  • Oncology

Cite this

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer. / On behalf of the Australian Ovarian Cancer Study Group.

In: Oncotarget, Vol. 7, No. 43, 2016, p. 69097-69110.

Research output: Contribution to journalArticle

On behalf of the Australian Ovarian Cancer Study Group. / Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer. In: Oncotarget. 2016 ; Vol. 7, No. 43. pp. 69097-69110.
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abstract = "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.",
keywords = "Biomarkers, Genetic variation, Immunosuppression, Ovarian cancer, TGFBR2",
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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 - Dürst, Matthias

AU - Pejovic, Tanja

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

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U2 - 10.18632/oncotarget.10215

DO - 10.18632/oncotarget.10215

M3 - Article

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SP - 69097

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JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

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