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

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 (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 135

Pages Range: 137-54

Journal Issue: 1

DOI: 10.1007/s00439-015-1616-8

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.

Authors with CRIS profile

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Roswell Park Cancer Institute United States (USA) (US) Mayo Clinic United States (USA) (US) University of Cambridge United Kingdom (GB) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) The University of Melbourne Australia (AU) Antoni van Leeuwenhoek Netherlands (NL) London School of Hygiene and Tropical Medicine United Kingdom (GB) King’s College London United Kingdom (GB) University of Oxford United Kingdom (GB) Ruprecht-Karls-Universität Heidelberg Germany (DE) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) Copenhagen University Hospital Denmark (DK) Hospital Monte Naranco Spain (ES) University of California Irvine United States (USA) (US) Beckman Research Institute of City of Hope (BRI) United States (USA) (US) Universitätsklinikum Köln Germany (DE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Université Laval (UL) Canada (CA) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Technische Universität München (TUM) Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) IFOM - FIRC Institute of Molecular Oncology Italy (IT) University of Southern California (USC) United States (USA) (US) McGill University Canada (CA) Vanderbilt University United States (USA) (US) Oulun Yliopisto / University of Oulo Finland (FI) Mount Sinai Hospital (MSH) Canada (CA) National Cancer Institute (NCI) United States (USA) (US) Karolinska Institute Sweden (SE) University of Sheffield United Kingdom (GB) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) The Institute of Cancer Research (ICR) United Kingdom (GB)

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.

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