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

• Published in: Breast cancer research and treatment Vol. 130; no. 3; pp. 939 - 951
• Main Authors: Sung, Hyuna, Lee, Kyoung-Mu, Choi, Ji-Yeob, Han, Sohee, Lee, Ji-Young, Li, Lian, Park, Sue K., Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Kang, Daehee
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2011; Springer; Springer Nature B.V
• Subjects: Adult; Biological and medical sciences; Biosynthesis; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer; Cancer research; Cancer therapies; Case-Control Studies; Development and progression; Epidemiology; Estrogen; Female; Gene Dosage; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genotype; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Menopause; MicroRNA; MicroRNAs - genetics; Middle Aged; Oncology; Oncology, Experimental; Polymorphism; Polymorphism, Single Nucleotide; Postmenopausal women; Progesterone; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Republic of Korea; Risk Factors; Tumors; Asia; Korea; Republic of Korea; South Korea; Hormone receptor status; Breast cancer; Single nucleotide polymorphism; Genetic susceptibility; MicroRNA biogenesis pathway; Human; Breast disease; RNA interference; Genetic variability; Micro RNA; Genotype; Malignant tumor; Case control study; Mammary gland diseases; Gene silencing; Gene; Risk factor; Genetics; Cancer; Hormonal receptor
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-011-1656-2

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.