MicroRNA related polymorphisms and breast cancer risk

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. W...

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Published in:PloS one 2014-11, Vol.9 (11), p.e109973
Main Authors: Khan, Sofia, Greco, Dario, Michailidou, Kyriaki, Milne, Roger L, Muranen, Taru A, Heikkinen, Tuomas, Aaltonen, Kirsimari, Dennis, Joe, Bolla, Manjeet K, Liu, Jianjun, Hall, Per, Irwanto, Astrid, Humphreys, Keith, Li, Jingmei, Czene, Kamila, Chang-Claude, Jenny, Hein, Rebecca, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Fletcher, Olivia, Peto, Julian, dos Santos Silva, Isabel, Johnson, Nichola, Gibson, Lorna, Aitken, Zoe, Hopper, John L, Tsimiklis, Helen, Bui, Minh, Makalic, Enes, Schmidt, Daniel F, Southey, Melissa C, Apicella, Carmel, Stone, Jennifer, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel A, van der Luijt, Rob B, Meindl, Alfons, Schmutzler, Rita K, Müller-Myhsok, Bertram, Lichtner, Peter, Turnbull, Clare, Rahman, Nazneen, Chanock, Stephen J, Hunter, David J, Cox, Angela, Cross, Simon S, Reed, Malcolm W R, Schmidt, Marjanka K, Broeks, Annegien, Van't Veer, Laura J, Hogervorst, Frans B, Fasching, Peter A, Schrauder, Michael G, Ekici, Arif B, Beckmann, Matthias W, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Benitez, Javier, Zamora, Pilar M, Perez, Jose I A, Haiman, Christopher A, Henderson, Brian E, Schumacher, Fredrick, Le Marchand, Loic, Pharoah, Paul D P, Dunning, Alison M, Shah, Mitul, Luben, Robert, Brown, Judith, Couch, Fergus J, Wang, Xianshu, Vachon, Celine, Olson, Janet E, Lambrechts, Diether, Moisse, Matthieu, Paridaens, Robert, Christiaens, Marie-Rose, Guénel, Pascal, Truong, Thérèse, Laurent-Puig, Pierre, Mulot, Claire, Marme, Frederick, Burwinkel, Barbara, Schneeweiss, Andreas, Sohn, Christof, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Andrulis, Irene L, Knight, Julia A, Tchatchou, Sandrine, Mulligan, Anna Marie, Dörk, Thilo, Bogdanova, Natalia V, Antonenkova, Natalia N
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Apoptosis
Binding Sites
Biology and Life Sciences
Breast cancer
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Cancer
Case-Control Studies
Child & adolescent psychiatry
Chromosome Mapping
Computational Biology
Confidence intervals
Consortia
Data processing
Epidemiology
Estrogen receptors
Estrogens
Female
Gene expression
Gene regulation
Genes
Genetic diversity
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Genotype
Gynecology
Health risk assessment
Health risks
Hospitals
Humans
Hygiene
Machinery
Machinery and equipment
Medical research
Medicin och hälsovetenskap
Medicine
Meta-analysis
MicroRNAs
MicroRNAs - genetics
miRNA
Obstetrics
Oncology
Ovarian cancer
Pathology
Polymorphism, Single Nucleotide
Population
Primary care
Public health
Receptors, Estrogen - metabolism
Ribonucleic acid
Risk
RNA
Single-nucleotide polymorphism
Subgroups
Target recognition
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Description
Summary:Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0109973