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Common genetic polymorphisms of microRNA biogenesis pathway genes and risk of breast cancer: a case-control study in Korea.

Abstract：

:Recent compelling evidence indicates that mutation, aberrant expression, and dysregulation of microRNA (miRNA) biogenesis are implicated in cancer development and progression. Based on the important role of miRNA biogenesis pathway in carcinogenesis, we hypothesized that genetic variations in this pathway genes may play a role as susceptibility factors for breast cancer. To test this hypothesis, we investigated the associations between 41 single nucleotide polymorphisms (SNPs) in 14 genes involved in miRNA biogenesis pathway and breast cancer risk in a case-control study of 559 Korean breast cancer cases and 567 controls frequency-matched by age. In all women, 3 SNPs (AGO1 rs595055, AGO2 rs3864659, and p68 rs1991401) were significantly associated with breast cancer risk. In stratified analysis by menopausal status, altered risk associations were observed for 7 SNPs in postmenopausal breast cancer. When subjects were grouped by the number of high-risk genotypes, we found a progressive increase in gene-dosage effect (P (trend) = 9.46E-7). The protective effects of AGO2 rs3864659 and HIWI rs11060845 were more pronounced in progesterone receptor-positive (PR+) cancer than in progesterone receptor-negative (PR-) cancer (odds ratio (OR), 0.50; 95% confidence interval (CI), 0.30-0.84 vs. OR, 0.94; 95% CI, 0.60-1.84; P (heterogeneity) = 0.04 and OR, 0.57; 95% CI, 0.37-0.88 vs. OR, 0.97; 95% CI, 0.65-1.44; P (heterogeneity) = 0.02, respectively), and the DROSHA rs644236 had stronger association with estrogen receptor-negative (ER-) cancer than for estrogen receptor-positive (ER+) cancer (OR, 1.39; 95% CI, 1.08-1.78 vs. OR, 1.05; 95% CI, 0.85-1.29; P (heterogeneity) = 0.04). Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer risk, and the modifiable effects might be different according to the menopausal status and hormone receptor status.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Sung H,Lee KM,Choi JY,Han S,Lee JY,Li L,Park SK,Yoo KY,Noh DY,Ahn SH,Kang D

doi

10.1007/s10549-011-1656-2

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

939-51

issue

3

eissn

0167-6806

issn

1573-7217

journal_volume

130

pub_type

杂志文章

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