Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer

被引：20

作者：

Goode, Ellen L. ^{[1
]}

DeRycke, Melissa ^{[1
]}

Kalli, Kimberly R. ^{[2
]}

Oberg, Ann L. ^{[1
]}

Cunningham, Julie M. ^{[3
]}

Maurer, Matthew J. ^{[1
]}

Fridley, Brooke L. ^{[1
]}

Armasu, Sebastian M. ^{[1
]}

Serie, Daniel J. ^{[1
]}

Ramar, Priya ^{[1
]}

Goergen, Krista ^{[1
]}

Vierkant, Robert A. ^{[1
]}

Rider, David N. ^{[1
]}

Sicotte, Hugues ^{[1
]}

Wang, Chen ^{[1
]}

Winterhoff, Boris ^{[7
]}

Phelan, Catherine M. ^{[18
]}

Schildkraut, Joellen M. ^{[8
]}

Weber, Rachel P. ^{[9
]}

Iversen, Ed ^{[10
]}

Berchuck, Andrew ^{[8
]}

Sutphen, Rebecca ^{[11
]}

Birrer, Michael J. ^{[12
]}

Hampras, Shalaka ^{[5
]}

Preus, Leah ^{[5
]}

Gayther, Simon A. ^{[13
]}

Ramus, Susan J. ^{[13
]}

Wentzensen, Nicolas ^{[14
]}

Yang, Hannah P. ^{[14
]}

Garcia-Closas, Montserrat ^{[15
]}

Song, Honglin ^{[16
]}

Tyrer, Jonathan ^{[16
]}

Pharoah, Paul P. D. ^{[16
]}

Konecny, Gottfried ^{[17
]}

Sellers, Thomas A. ^{[18
]}

Ness, Roberta B. ^{[6
]}

Sucheston, Lara E. ^{[5
]}

Odunsi, Kunle ^{[4
]}

Hartmann, Lynn C. ^{[2
]}

Moysich, Kirsten B. ^{[5
]}

Knutson, Keith L. ^{[19
]}

机构：

[1] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Med Oncol, Rochester, MN USA

[3] Mayo Clin, Dept Expt Pathol, Rochester, MN USA

[4] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA

[5] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[6] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA

[7] Mayo Clin, Dept Gynecol Oncol, Rochester, MN USA

[8] Duke Univ, Duke Comprehens Canc Ctr, Durham, NC USA

[9] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA

[10] Duke Univ, Dept Stat Sci, Durham, NC USA

[11] Univ S Florida, Coll Med, Tampa, FL USA

[12] Brigham & Womens Hosp, Boston, MA 02115 USA

[13] Univ So Calif, Los Angeles, CA USA

[14] NCI, Bethesda, MD 20892 USA

[15] Inst Canc Res, Sutton, Surrey, England

[16] Univ Cambridge, Cambridge, England

[17] Univ Calif Los Angeles, Dept Gynecol Oncol, Los Angeles, CA USA

[18] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA

[19] Mayo Clin, Dept Immunol, Rochester, MN USA

来源：

PLOS ONE | 2013年 / 8卷 / 01期

基金：

英国医学研究理事会;

关键词：

TGF-BETA; MEDIATED SUPPRESSION; OX40; COSTIMULATION; IMMUNE SUPPRESSION; EXPRESSION; SURVIVAL; RECEPTOR; WOMEN; FOXP3; GITR;

D O I：

10.1371/journal.pone.0053903

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7x10(-5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5x10(-4), and rs3753348, p = 9.0x10(-4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0x10(-4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1x10(-4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies.

引用

页数：7

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