Yinhua Zhu

A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer

Abstract The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34–0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64–0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43–0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.

Association of IL-1B Gene Polymorphisms with Nasopharyngeal Carcinoma in a Chinese Population

AIMS Interleukin-1beta (IL-1beta) is a multifunctional cytokine that up-regulates the inflammatory response and participates in carcinogenesis, malignant transformation, tumour growth, invasion and metastasis. The IL-1B gene, encoding IL-1beta cytokine, contains several single nucleotide polymorphisms. Previous studies have shown that the polymorphisms of this gene may be associated with an increased risk of some cancers. However, no specific genetic risk factor for nasopharyngeal carcinoma (NPC) has been identified so far and there is no report of the IL-1B gene polymorphisms in relation to NPC. The aim of this study was to test whether the promoter polymorphisms in the IL-1B gene are associated with the risk of NPC. MATERIALS AND METHODS Two single nucleotide polymorphisms of IL-1B gene (-511C/T and -31T/C) in 113 patients with NPC and 144 age- and sex-matched controls in a Chinese population were analysed using a polymerase chain reaction-restriction fragment length polymorphism strategy. RESULTS The IL-1B-31 and -511 loci were in highly linkage disequilibrium, and the -511T allele carriers were associated with a significantly increased risk of NPC as compared with the non-carriers (odds ratio=1.53, 95% confidence interval=1.07-2.17, P=0.018). Genotypes and allele frequencies at the IL-1B-31 locus in NPC cases were not different from the controls. Haplotype analysis showed that the -511T/-31T haplotype of the IL-1B gene conveyed the high risk for NPC compared with the -511C/-31T haplotype (odds ratio=17.09, 95% confidence interval=5.90-49.56, P<0.001). CONCLUSION This is the first report describing the association between IL-1B gene polymorphisms and NPC, and our data suggest that the IL-1B-511C/T polymorphism and the -511T/-31T haplotype may contribute to the risk of developing NPC in the Chinese population.

Discovery and biological characterization of a novel series of androgen receptor modulators: Novel modulators of androgen receptors

Selective androgen receptor modulators are of great value in the treatment of prostate cancer. The purpose of this study was to provide a preliminary characterization of a new class of non‐steroidal androgen receptor modulators discovered in a high‐throughput screening campaign.