TY - JOUR
T1 - Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer
AU - Goode, Ellen L.
AU - DeRycke, Melissa
AU - Kalli, Kimberly R.
AU - Oberg, Ann L.
AU - Cunningham, Julie M.
AU - Maurer, Matthew J.
AU - Fridley, Brooke L.
AU - Armasu, Sebastian M.
AU - Serie, Daniel J.
AU - Ramar, Priya
AU - Goergen, Krista
AU - Vierkant, Robert A.
AU - Rider, David N.
AU - Sicotte, Hugues
AU - Wang, Chen
AU - Winterhoff, Boris
AU - Phelan, Catherine M.
AU - Schildkraut, Joellen M.
AU - Weber, Rachel P.
AU - Iversen, Ed
AU - Berchuck, Andrew
AU - Sutphen, Rebecca
AU - Birrer, Michael J.
AU - Hampras, Shalaka
AU - Preus, Leah
AU - Gayther, Simon A.
AU - Ramus, Susan J.
AU - Wentzensen, Nicolas
AU - Yang, Hannah P.
AU - Garcia-Closas, Montserrat
AU - Song, Honglin
AU - Tyrer, Jonathan
AU - Pharoah, Paul P D
AU - Konecny, Gottfried
AU - Sellers, Thomas A.
AU - Ness, Roberta B.
AU - Sucheston, Lara E.
AU - Odunsi, Kunle
AU - Hartmann, Lynn C.
AU - Moysich, Kirsten B.
AU - Knutson, Keith L.
PY - 2013/1/30
Y1 - 2013/1/30
N2 - 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 = 2.7×10-5), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10-4, and rs3753348, p = 9.0×10-4, respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10-4). 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 = 8.1×10-4) 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.
AB - 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 = 2.7×10-5), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10-4, and rs3753348, p = 9.0×10-4, respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10-4). 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 = 8.1×10-4) 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.
UR - http://www.scopus.com/inward/record.url?scp=84873863148&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873863148&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0053903
DO - 10.1371/journal.pone.0053903
M3 - Article
C2 - 23382860
AN - SCOPUS:84873863148
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 1
M1 - e53903
ER -
