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Title: No evidence for association of inherited variation in genes involved in mitosis and percent mammographic density
Authors: Vachon, C.M
Li, J 
Scott, C.G
Hall, P
Czene, K
Wang, X
Liu, J
Fredericksen, Z.S
Rider, D.N
Wu, F.-F
Olson, J.E
Cunningham, J.M
Stevens, K.N
Sellers, T.A
Pankratz, S.V
Couch, F.J
Keywords: aurora B kinase
maintenance complex component 3
prpf4 protein
unclassified drug
body mass
controlled study
gene control
gene locus
genetic association
genetic variability
major clinical study
single nucleotide polymorphism
breast tumor
case control study
congenital malformation
mammary gland
mammographic density
middle aged
single nucleotide polymorphism
statistical model
Breast Neoplasms
Case-Control Studies
Genetic Association Studies
Linear Models
Mammary Glands, Human
Middle Aged
Polymorphism, Single Nucleotide
Issue Date: 2012
Citation: Vachon, C.M, Li, J, Scott, C.G, Hall, P, Czene, K, Wang, X, Liu, J, Fredericksen, Z.S, Rider, D.N, Wu, F.-F, Olson, J.E, Cunningham, J.M, Stevens, K.N, Sellers, T.A, Pankratz, S.V, Couch, F.J (2012). No evidence for association of inherited variation in genes involved in mitosis and percent mammographic density. Breast Cancer Research 14 (1) : R7. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Introduction: Increased mammographic breast density is one of the strongest risk factors for breast cancer. While two-thirds of the variation in mammographic density appears to be genetically influenced, few variants have been identified. We examined the association of inherited variation in genes from pathways that mediate cell division with percent mammographic density (PMD) adjusted for age, body mass index (BMI) and postmenopausal hormones, in two studies of healthy postmenopausal women.Methods: We investigated 2,058 single nucleotide polymorphisms (SNPs) in 378 genes involved in regulation of mitosis for associations with adjusted PMD among 484 unaffected postmenopausal controls (without breast cancer) from the Mayo Clinic Breast Cancer Study (MCBCS) and replicated the findings in postmenopausal controls (n = 726) from the Singapore and Sweden Breast Cancer Study (SASBAC) study. PMD was assessed in both studies by a computer-thresholding method (Cumulus) and linear regression approaches were used to assess the association of SNPs and PMD, adjusted for age, BMI and postmenopausal hormones. A P-value threshold of 4.2 × 10 -5based on a Bonferroni correction of effective number of independent tests was used for statistical significance. Further, a pathway-level analysis was conducted of all 378 genes using the self-contained gene-set analysis method GLOSSI.Results: A variant in PRPF4, rs10733604, was significantly associated with adjusted PMD in the MCBCS (P = 2.7 × 10 -7), otherwise, no single SNP was associated with PMD. Additionally, the pathway analysis provided no evidence of enrichment in the number of associations observed between SNPs in the mitotic genes and PMD (P = 0.60). We evaluated rs10733604 (PRPF4), and 73 other SNPs at P < 0.05 from 51 genes in the SASBAC study. There was no evidence of an association of rs10733604 (PRPF4) with adjusted PMD in SASBAC (P = 0.23). There were, however, consistent associations (P < 0.05) of variants at the putative locus, LOC375190, Aurora B kinase (AURKB), and Mini-chromosome maintenance complex component 3 (MCM3) with adjusted PMD, although these were not statistically significant.Conclusions: Our findings do not support a role of inherited variation in genes involved in regulation of cell division and adjusted percent mammographic density in postmenopausal women. © 2012 Vachon et al.; licensee BioMed Central Ltd.
Source Title: Breast Cancer Research
ISSN: 14655411
DOI: 10.1186/bcr3088
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications

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