Variations of DICER1 sequence in Chinese women with BRCA1/BRCA2 negative familial breast cancer.
e12557 Background: Germline mutations in identified breast cancer susceptibility genes account for less than 20% of Chinese familial breast cancers. Dicer is an essential component of the microRNA producing machinery and germline mutations of DICER1 gene have been confirmed in familial pleuropulmonary blastoma, ovarian sex cord-stromal tumor and so on. Moreover, low expression of DICER1 is frequently detected in breast cancer. However, whether germline mutations of DICER1 occur in familial breast cancers remains unknown. Methods: 65 breast cancer probands from BRCA1/BRCA2 negative Chinese breast cancer families were used for screening of germline mutations in DICER1. In addition, 100 unrelated healthy females were enrolled as the controls. Polymerase chain reaction (PCR)-sequencing assay was employed to screen mutations in the entire coding regions and exon-intron boundaries of DICER1. Genotype and haplotype analyses were studied by widely available programs. Results: No deleterious mutations were identified in the 65 breast cancer probands. However, we found 12 germline variations and 4 of which were novel. In addition, the G allele frequency of rs2297730 (IVS12-91 A>G) was higher in familial breast cancer patients group than that in healthy controls group (OR = 1.873, 95% CI: 1.174-2.988, P = 0.008), and the A/G genotype were significantly associated with familial breast cancer (OR = 3.133; 95% CI: 1.562-6.287, P = 0.004). According to the minimum value of Akaike’s Information Criterion (AIC), the best genetic model was dominant. In addition, the haplotype GCGGAT was significantly associated with familial breast cancer (OR = 2.17, 95% CI: 1.20-3.91, P = 0.011). Conclusions: Although none of deleterious mutations were identified in the DICER1 gene, the current study provided a haplotype analysis of the DICER1 gene polymorphisms. We showed a significantly increased risk of BRCA1/BRCA2 negative familial breast cancer for DICER1 IVS12-91 A>G variant. It might be a potential risk marker for breast cancer in thus population.