Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival.
BACKGROUND
Although 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.


METHODS
We 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.


RESULTS
Seven 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).


CONCLUSIONS
Our 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.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
Hyuna
H
Sung
Sujee
S
Jeon
Kyoung-Mu
KM
Lee
Sohee
S
Han
Minkyo
M
Song
Ji-Yeob
JY
Choi
Sue K
SK
Park
Keun-Young
KY
Yoo
Dong-Young
DY
Noh
Sei-Hyun
SH
Ahn
Daehee
D
Kang
D000328:Adult; D060565:Argonaute Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D053487:DEAD-box RNA Helicases / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D043244:Ribonuclease III / Q000235:genetics
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases