Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium

Journal article


Publication Details

Author(s): Lei J, Rudolph A, Moysich KB, Behrens S, Goode EL, Bolla MK, Dennis J, Dunning AM, Easton DF, Wang Q, Benitez J, Hopper JL, Southey MC, Schmidt MK, Broeks A, Fasching P, Häberle L, Peto J, Dos-Santos-Silva I, Sawyer EJ, Tomlinson I, Burwinkel B, Marme F, Guenel P, Truong T, Bojesen SE, Flyger H, Nielsen SF, Nordestgaard BG, Gonzalez-Neira A, Menendez P, Anton-Culver H, Neuhausen SL, Brenner H, Arndt V, Meindl A, Schmutzler RK, Brauch H, Hamann U, Nevanlinna H, Fagerholm R, Doerk T, Bogdanova NV, Mannermaa A, Hartikainen JM, Van Dijck L, Smeets A, Flesch-Janys D, Eilber U, Radice P, Peterlongo P, Couch FJ, Hallberg E, Giles GG, Milne RL, Haiman CA, Schumacher F, Simard J, Goldberg MS, Kristensen V, Borresen-Dale AL, Zheng W, Beeghly-Fadiel A, Winqvist R, Grip M, Andrulis IL, Glendon G, Garcia-Closas M, Figueroa J, Czene K, Brand JS, Darabi H, Eriksson M, Hall P, Li J, Cox A, Cross SS, Pharoah PDP, Shah M, Kabisch M, Torres D, Jakubowska A, Lubinski J, Ademuyiwa F, Ambrosone CB, Swerdlow A, Jones M, Chang-Claude J
Journal: Human genetics
Publication year: 2016
Volume: 135
Journal issue: 1
Pages range: 137-54
ISSN: 0340-6717
eISSN: 1432-1203


Abstract

Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.


FAU Authors / FAU Editors

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


External institutions with authors

Antoni van Leeuwenhoek
Beckman Research Institute of City of Hope (BRI)
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Fondazione IRCCS: Istituto Nazionale dei Tumori
Helsingin yliopisto / University of Helsinki
Hospital Monte Naranco
IFOM - FIRC Institute of Molecular Oncology
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
King’s College London
Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri
London School of Hygiene and Tropical Medicine
Mayo Clinic
McGill University
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
Oslo University Hospital / Oslo Universitetssykehus
Oulun Yliopisto / University of Oulo
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
Roswell Park Cancer Institute
Ruprecht-Karls-Universität Heidelberg
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Technische Universität München (TUM)
The Institute of Cancer Research (ICR)
The University of Melbourne
Universitätsklinikum Hamburg-Eppendorf (UKE)
Universitätsklinikum Köln
Université Laval (UL)
University of California Irvine
University of Cambridge
University of Oxford
University of Sheffield
University of Southern California (USC)
Vanderbilt University


How to cite

APA:
Lei, J., Rudolph, A., Moysich, K.B., Behrens, S., Goode, E.L., Bolla, M.K.,... Chang-Claude, J. (2016). Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium. Human genetics, 135(1), 137-54. https://dx.doi.org/10.1007/s00439-015-1616-8

MLA:
Lei, Jieping, et al. "Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium." Human genetics 135.1 (2016): 137-54.

BibTeX: 

Last updated on 2019-21-07 at 07:52