Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome

AOCS Group

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Abstract

The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 × 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 × 10(-5)), rs2476491 (HR, = 1.40; 95% CI, 1.19-1.64; P = 5.6 × 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 × 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 × 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.

Original languageEnglish (US)
Pages (from-to)332-340
Number of pages9
JournalCancer immunology research
Volume2
Issue number4
DOIs
StatePublished - Apr 1 2014

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Regulatory T-Lymphocytes
Ovarian Neoplasms
Single Nucleotide Polymorphism
Confidence Intervals
Survival
Genes
Transforming Growth Factor beta3
Galectin 1
Endometrioid Carcinoma
Mucinous Adenocarcinoma
Interleukin-15
Oral Contraceptives
Interleukin-8
Interleukin-10
Interleukin-6
Neoplasms
Alleles
Genotype
Carcinoma
Amino Acids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome. / AOCS Group.

In: Cancer immunology research, Vol. 2, No. 4, 01.04.2014, p. 332-340.

Research output: Contribution to journalArticle

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title = "Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome",
abstract = "The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95{\%} confidence interval (CI), 1.22-1.64; P = 5.7 × 10(-6)], rs791587 (HR, 1.36; 95{\%} CI, 1.17-1.57; P = 6.2 × 10(-5)), rs2476491 (HR, = 1.40; 95{\%} CI, 1.19-1.64; P = 5.6 × 10(-5)), and rs10795763 (HR, 1.35; 95{\%} CI, 1.17-1.57; P = 7.9 × 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95{\%} CI, 0.54-0.82; P = 9.3 × 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.",
author = "{AOCS Group} and Bridget Charbonneau and Moysich, {Kirsten B.} and Kalli, {Kimberly R.} and Oberg, {Ann L.} and Vierkant, {Robert A.} and Fogarty, {Zachary C.} and Block, {Matthew S.} and Maurer, {Matthew J.} and Goergen, {Krista M.} and Fridley, {Brooke L.} and Cunningham, {Julie M.} and Rider, {David N.} and Claudia Preston and Hartmann, {Lynn C.} and Kate Lawrenson and Chen Wang and Jonathan Tyrer and Honglin Song and Anna deFazio and Johnatty, {Sharon E.} and Doherty, {Jennifer A.} and Phelan, {Catherine M.} and Sellers, {Thomas A.} and Ramirez, {Starr M.} and Vitonis, {Allison F.} and Terry, {Kathryn L.} and {Van Den Berg}, David and Pike, {Malcolm C.} and Wu, {Anna H.} and Andrew Berchuck and Aleksandra Gentry-Maharaj and Ramus, {Susan J.} and Brenda Diergaarde and Howard Shen and Allan Jensen and Janusz Menkiszak and Cezary Cybulski and Jan Lubiłski and Argyrios Ziogas and Rothstein, {Joseph H.} and Valerie McGuire and Weiva Sieh and Jenny Lester and Christine Walsh and Ignace Vergote and Sandrina Lambrechts and Evelyn Despierre and Montserrat Garcia-Closas and Hannah Yang and Tanja Pejovic",
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T1 - Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome

AU - AOCS Group

AU - Charbonneau, Bridget

AU - Moysich, Kirsten B.

AU - Kalli, Kimberly R.

AU - Oberg, Ann L.

AU - Vierkant, Robert A.

AU - Fogarty, Zachary C.

AU - Block, Matthew S.

AU - Maurer, Matthew J.

AU - Goergen, Krista M.

AU - Fridley, Brooke L.

AU - Cunningham, Julie M.

AU - Rider, David N.

AU - Preston, Claudia

AU - Hartmann, Lynn C.

AU - Lawrenson, Kate

AU - Wang, Chen

AU - Tyrer, Jonathan

AU - Song, Honglin

AU - deFazio, Anna

AU - Johnatty, Sharon E.

AU - Doherty, Jennifer A.

AU - Phelan, Catherine M.

AU - Sellers, Thomas A.

AU - Ramirez, Starr M.

AU - Vitonis, Allison F.

AU - Terry, Kathryn L.

AU - Van Den Berg, David

AU - Pike, Malcolm C.

AU - Wu, Anna H.

AU - Berchuck, Andrew

AU - Gentry-Maharaj, Aleksandra

AU - Ramus, Susan J.

AU - Diergaarde, Brenda

AU - Shen, Howard

AU - Jensen, Allan

AU - Menkiszak, Janusz

AU - Cybulski, Cezary

AU - Lubiłski, Jan

AU - Ziogas, Argyrios

AU - Rothstein, Joseph H.

AU - McGuire, Valerie

AU - Sieh, Weiva

AU - Lester, Jenny

AU - Walsh, Christine

AU - Vergote, Ignace

AU - Lambrechts, Sandrina

AU - Despierre, Evelyn

AU - Garcia-Closas, Montserrat

AU - Yang, Hannah

AU - Pejovic, Tanja

PY - 2014/4/1

Y1 - 2014/4/1

N2 - The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 × 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 × 10(-5)), rs2476491 (HR, = 1.40; 95% CI, 1.19-1.64; P = 5.6 × 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 × 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 × 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.

AB - The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 × 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 × 10(-5)), rs2476491 (HR, = 1.40; 95% CI, 1.19-1.64; P = 5.6 × 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 × 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 × 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer.

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