Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Bridget Charbonneau; Kirsten B Moysich; Kimberly R Kalli; Ann L Oberg; Robert A Vierkant; Zachary C Fogarty; Matthew S Block; Matthew J Maurer; Krista M Goergen; Brooke L Fridley; Julie M Cunningham; David N Rider; Claudia Preston; Lynn C Hartmann; Kate Lawrenson; Chen Wang; Jonathan Tyrer; Honglin Song; Anna deFazio; Sharon E Johnatty; Jennifer A Doherty; Catherine M Phelan; Thomas A Sellers; Starr M Ramirez; Allison F Vitonis; Kathryn L Terry; David Van Den Berg; Malcolm C Pike; Anna H Wu; Andrew Berchuck; Aleksandra Gentry-Maharaj; Susan J Ramus; Brenda Diergaarde; Howard Shen; Allan Jensen; Janusz Menkiszak; Cezary Cybulski; Jan Lubiłski; Argyrios Ziogas; Joseph H Rothstein; Valerie McGuire; Weiva Sieh; Jenny Lester; Christine Walsh; Ignace Vergote; Sandrina Lambrechts; Evelyn Despierre; Montserrat Garcia-Closas; Claus K Hogdall; Susanne K Kjaer; AOCS Group

doi:10.1158/2326-6066.CIR-13-0136

Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Bridget Charbonneau, Kirsten B Moysich, Kimberly R Kalli, Ann L Oberg, Robert A Vierkant, Zachary C Fogarty, Matthew S Block, Matthew J Maurer, Krista M Goergen, Brooke L Fridley, Julie M Cunningham, David N Rider, Claudia Preston, Lynn C Hartmann, Kate Lawrenson, Chen Wang, Jonathan Tyrer, Honglin Song, Anna deFazio, Sharon E JohnattyJennifer A Doherty, Catherine M Phelan, Thomas A Sellers, Starr M Ramirez, Allison F Vitonis, Kathryn L Terry, David Van Den Berg, Malcolm C Pike, Anna H Wu, Andrew Berchuck, Aleksandra Gentry-Maharaj, Susan J Ramus, Brenda Diergaarde, Howard Shen, Allan Jensen, Janusz Menkiszak, Cezary Cybulski, Jan Lubiłski, Argyrios Ziogas, Joseph H Rothstein, Valerie McGuire, Weiva Sieh, Jenny Lester, Christine Walsh, Ignace Vergote, Sandrina Lambrechts, Evelyn Despierre, Montserrat Garcia-Closas, Claus K Hogdall, Susanne K Kjaer, AOCS Group

Department of Clinical Medicine

18 Citations (Scopus)

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 rs 10795763(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) 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 language	English
Journal	Cancer Immunology Research (CIR)
Volume	2
Issue number	4
Pages (from-to)	332-340
Number of pages	9
ISSN	2326-6066
DOIs	https://doi.org/10.1158/2326-6066.CIR-13-0136
Publication status	Published - Apr 2014

Keywords

Female
Gene Expression
Gene Expression Profiling
Genetic Predisposition to Disease
Genetic Variation
Germ-Line Mutation
Humans
Interleukin-2 Receptor alpha Subunit
Neoplasm Grading
Neoplasm Invasiveness
Ovarian Neoplasms
Patient Outcome Assessment
Polymorphism, Single Nucleotide
Prognosis
T-Lymphocytes, Regulatory

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/2326-6066.CIR-13-0136

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Charbonneau, B., Moysich, K. B., Kalli, K. R., Oberg, A. L., Vierkant, R. A., Fogarty, Z. C., Block, M. S., Maurer, M. J., Goergen, K. M., Fridley, B. L., Cunningham, J. M., Rider, D. N., Preston, C., Hartmann, L. C., Lawrenson, K., Wang, C., Tyrer, J., Song, H., deFazio, A., ... AOCS Group (2014). Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome. Cancer Immunology Research (CIR), 2(4), 332-340. https://doi.org/10.1158/2326-6066.CIR-13-0136

Charbonneau, B, Moysich, KB, Kalli, KR, Oberg, AL, Vierkant, RA, Fogarty, ZC, Block, MS, Maurer, MJ, Goergen, KM, Fridley, BL, Cunningham, JM, Rider, DN, Preston, C, Hartmann, LC, Lawrenson, K, Wang, C, Tyrer, J, Song, H, deFazio, A, Johnatty, SE, Doherty, JA, Phelan, CM, Sellers, TA, Ramirez, SM, Vitonis, AF, Terry, KL, Van Den Berg, D, Pike, MC, Wu, AH, Berchuck, A, Gentry-Maharaj, A, Ramus, SJ, Diergaarde, B, Shen, H, Jensen, A, Menkiszak, J, Cybulski, C, Lubiłski, J, Ziogas, A, Rothstein, JH, McGuire, V, Sieh, W, Lester, J, Walsh, C, Vergote, I, Lambrechts, S, Despierre, E, Garcia-Closas, M, Hogdall, CK , Kjaer, SK & AOCS Group 2014, 'Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome', Cancer Immunology Research (CIR), vol. 2, no. 4, pp. 332-340. https://doi.org/10.1158/2326-6066.CIR-13-0136

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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 rs 10795763(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) 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.",

keywords = "Female, Gene Expression, Gene Expression Profiling, Genetic Predisposition to Disease, Genetic Variation, Germ-Line Mutation, Humans, Interleukin-2 Receptor alpha Subunit, Neoplasm Grading, Neoplasm Invasiveness, Ovarian Neoplasms, Patient Outcome Assessment, Polymorphism, Single Nucleotide, Prognosis, T-Lymphocytes, Regulatory",

author = "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 Lubi{\l}ski 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 Hogdall, {Claus K} and Kjaer, {Susanne K} and {AOCS Group}",

year = "2014",

month = apr,

doi = "10.1158/2326-6066.CIR-13-0136",

language = "English",

volume = "2",

pages = "332--340",

journal = "Cancer Immunology Research",

issn = "2326-6066",

publisher = "American Association for Cancer Research",

number = "4",

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TY - JOUR

T1 - Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

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 - Hogdall, Claus K

AU - Kjaer, Susanne K

AU - AOCS Group

PY - 2014/4

Y1 - 2014/4

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 rs 10795763(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) 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 rs 10795763(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) 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.

KW - Female

KW - Gene Expression

KW - Gene Expression Profiling

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Germ-Line Mutation

KW - Humans

KW - Interleukin-2 Receptor alpha Subunit

KW - Neoplasm Grading

KW - Neoplasm Invasiveness

KW - Ovarian Neoplasms

KW - Patient Outcome Assessment

KW - Polymorphism, Single Nucleotide

KW - Prognosis

KW - T-Lymphocytes, Regulatory

U2 - 10.1158/2326-6066.CIR-13-0136

DO - 10.1158/2326-6066.CIR-13-0136

M3 - Journal article

C2 - 24764580

SN - 2326-6066

VL - 2

SP - 332

EP - 340

JO - Cancer Immunology Research

JF - Cancer Immunology Research

IS - 4

ER -

Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Abstract

Keywords

UN SDGs

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