Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survivalReport as inadecuate




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BMC Cancer

, 12:195

First Online: 28 May 2012Received: 16 December 2011Accepted: 28 May 2012DOI: 10.1186-1471-2407-12-195

Cite this article as: Sung, H., Jeon, S., Lee, KM. et al. BMC Cancer 2012 12: 195. doi:10.1186-1471-2407-12-195

Abstract

BackgroundAlthough the role of microRNA’s miRNA’s biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown.

MethodsWe used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms SNPs and both disease free survival DFS and overall survival OS among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died.

ResultsSeven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 rs11786030 and rs2292779 and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI rs4759659 and rs11060845 and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression 95% confidence interval CI, 1.41-4.88 and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death 95% CI, 1.52-5.69. We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 95% CI, 1.18- 3.93 and 4.47 95% CI, 2.45- 8.14, respectively P for trend, 6.11E-07.

ConclusionsOur results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.

KeywordsmicroRNA biogenesis pathway Breast cancer Survival Single nucleotide polymorphism AbbreviationsBMIBody mass index

CEUCEPH European ancestry

CHBHan Chinese in Beijing, China

CIConfidence interval

DFSDisease-free survival

EREstrogen receptor-positive

EREstrogen receptor-negative

GWA studyGenome-wide association study

HWEHardy-Weinberg equilibrium

JPTJapanese in Tokyo

LDLinkage disequilibrium

MAFMinor allele frequency

MiRNAmicroRNA

HRHazard ratio

OSOverall survival

PRProgesterone receptor-positive

PRProgesterone receptor-negative

SNPSingle nucleotide polymorphism.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-12-195 contains supplementary material, which is available to authorized users.

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Author: Hyuna Sung - Sujee Jeon - Kyoung-Mu Lee - Sohee Han - Minkyo Song - Ji-Yeob Choi - Sue K Park - Keun-Young Yoo - Dong-You

Source: https://link.springer.com/



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