Zhou Wg

Genetic polymorphisms in cytochrome P450 genes are associated with an increased risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population.

The purpose of this study was to examine whether functional polymorphisms in the cytochrome P450 (CYP) enzyme genes affect the risk of developing larynx and hypopharynx squamous cell carcinoma (SCC). We investigated CYP1A1, CYP1B1, CYP2E1, and CYP3A4 polymorphisms in 278 patients with laryngeal and hypopharyngeal SCC and 278 control subjects by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with the CYP1A1 3798CC or TC genotype had an odds ratio (OR) of 3.26 (95% confidence interval CI=1.76-6.03) or 1.56 (95% CI=1.06-2.31), compared with those with the TT genotype. An increased risk was also associated with the CYP1A1 462Val/Val genotype (OR=2.39, 95% CI=1.11-5.16), compared with the TT genotype. Haplotype analysis suggested a synergistic effect of these two polymorphisms. A multiplicative joint effect between the CYP1A1 3798T>C polymorphism and smoking was observed. The OR (95% CI) of the TC or CC genotype for nonsmokers and smokers of >20 pack-years were 1.85 (0.99-3.44) or 8.15 (4.35-15.26), respectively (P(trend)<0.05). The CYP1A1 single-nucleotide polymorphisms are associated with an increased risk of developing smoking-related laryngeal and hypopharyngeal SCC in a Han Chinese population.

Lentivirus‑delivered nemo‑like kinase small interfering RNA inhibits laryngeal cancer cell proliferation in vitro

Laryngeal squamous cell carcinoma is the most common form of head and neck squamous cell carcinoma. Multiple approaches have been applied to treat this type of cancer; however, no significant improvement in survival rate has been achieved. In the present study, the role of nemo-like kinase (NLK) in human laryngeal carcinoma Hep-2 cells was investigated. NLK has been identified as an important regulator of cell growth, patterning and cell death in a variety of organisms. Lentivirus-mediated-shRNA was employed to silence endogenous NLK expression. Downregulation of the expression of NLK following lentivirus infection was confirmed using reverse transcription quantitative polymerase chain reaction and western blot analysis. The effects of NLK downregulation on Hep-2 cell proliferation and cell cycle progression were analyzed using an MTT assay and flow cytometry, respectively. Downregulation of NLK also inhibited tumorigenesis and regulated the expression of cell cycle protein expression levels. Therefore, it was hypothesized that NLK is necessary for cell survival and tumorigenesis in laryngeal cancer cells. Furthermore, the absence of NLK may lead to cancer cell death. Collectively, the results of the present study demonstrated that the lentivirus-mediated targeted disruption of NLK may be a promising therapeutic method for the treatment of laryngeal cancer.