Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01

AUTHORS

Jieping Lei, Anja Rudolph, Kirsten B. Moysich, Sabine Behrens, Ellen L. Goode, Manjeet K. Bolla, Joe Dennis, Alison M. Dunning, Douglas F. Easton, Qin Wang, Javier Benitez, John L. Hopper, Melissa C. Southey, Marjanka K. Schmidt, Annegien Broeks, Peter A. Fasching, Lothar Haeberle, Julian Peto, Isabel dos-Santos-Silva, Elinor J. Sawyer, Ian Tomlinson, Barbara Burwinkel, Frederik Marmé, Pascal Guénel, Thérèse Truong, Stig E. Bojesen, Henrik Flyger, Sune F. Nielsen, Børge G. Nordestgaard, Anna González-Neira, Primitiva Menéndez, Hoda Anton-Culver, Susan L. Neuhausen, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K. Schmutzler, Hiltrud Brauch, Ute Hamann, Heli Nevanlinna, Rainer Fagerholm, Thilo Dörk, Natalia V. Bogdanova, Arto Mannermaa, Jaana M. Hartikainen, Australian Ovarian Study Group, kConFab Investigators, Laurien Van Dijck, Ann Smeets, Dieter Flesch-Janys, Ursula Eilber, Paolo Radice, Paolo Peterlongo, Fergus J. Couch, Emily Hallberg, Graham G. Giles, Roger L. Milne, Christopher A. Haiman, Fredrick Schumacher, Jacques Simard, Mark S. Goldberg, Vessela Kristensen, Anne-Lise Borresen-Dale, Wei Zheng, Alicia Beeghly-Fadiel, Robert Winqvist, Mervi Grip, Irene L. Andrulis, Gord Glendon, Montserrat García-Closas, Jonine Figueroa, Kamila Czene, Judith S. Brand, Hatef Darabi, Mikael Eriksson, Per Hall, Jingmei Li, Angela Cox, Simon S. Cross, Paul D. P. Pharoah, Mitul Shah, Maria Kabisch, Diana Torres, Anna Jakubowska, Jan Lubinski, Foluso Ademuyiwa, Christine B. Ambrosone, Anthony Swerdlow, Michael Jones, Jenny Chang-Claude

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. More... »

PAGES

137-154

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  • Journal

    TITLE

    Human Genetics

    ISSUE

    1

    VOLUME

    135

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00439-015-1616-8

    DOI

    http://dx.doi.org/10.1007/s00439-015-1616-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1051869077

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26621531


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