Germline mutations in the VHL gene associated with 3 different renal lesions in a Chinese von Hippel-Lindau disease family

Von Hippel–Lindau (VHL) disease is a rare autosomal dominant inherited cancer syndrome that is characterized by hemangioblastomas in the central nervous system and retina, renal cell carcinoma and cysts, pancreatic tumors and cysts, and pheochromocytoma. The underlying gene in this disease is the VHL tumor suppressor gene. We characterized a family with 2 affected siblings. The brother and sister displayed VHL type 2B and type 2A features, respectively. Renal lesions in the brother exhibited 3 different phenotypes, including simple renal cysts, multilocular cystic renal cell carcinoma and clear cell renal cell carcinoma. The phenotypes of the 3 concurrent renal lesions were first reported in this study. Mutation detection of the VHL gene revealed 2 recurrent mutations, namely c.256C>T (p.P86S) and c.340 + 5G > C. The former was predicted to be deleterious and to destabilize the hydrophobic core and lead to VHL dysfunction; however, the latter was predicted to be a benign variant. Our findings provided new data for the genotype-phenotype of VHL diseases and elucidated the pathogenic mechanism with in silico analysis.     

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??OBJECTIVE To explore the correlation between genetic polymorphism of folylpolyglutamate synthetase (FPGS),plasma concentrations of methotrexate (MTX) and prognosis in patients with acute leukemia. METHODS PCR-restriction fragment length polymophism(PCR-RFLP) was used to detect the genetic polymorphisms of FPGS rs1544105 in ALL patients(n=57) and the control individual(n=31). The plasma concentrations of MTX were measured by high performance liquid chromatography (HPLC) at the times of 24 and 44 h. The association between targeted polymorphisms and MTX concentration-to-dose (C/D) ratios was assessed. According to the result of follow up, survival curve was analyzed. RESULTS Similar frequencies of genotypes and alleles were found at FPGS rs1544105 in healthy subjects and ALL patients. In the genotype of AA, MTX C/D ratio at the time of 24 h was higher than the others (P<0.05).While there was not a significant difference at 44 h(P>0.05). Kaplan-Meier survival analysis showed that median survival time of AA genotype was longer than others. Overall survival(OS) rate was statistically different(P<0.05). CONCLUSION Folylpolyglutamate synthetase (FPGS) genetic polymorphism may be a useful method to predict the effectiveness of methotrexate.     

Polymorphisms in the vitamin D receptor (VDR) genes and skin cancer risk in European population: a meta-analysis

There have been a few epidemiological studies reporting VDR polymorphisms including Fok1, Bsm1, Apa1 and Taq1 with skin cancer incidence and, therefore, risk. The results, however, are controversial, often due to smaller sample size. Concerning most of the studies were performed on Caucasian population, we conducted this comprehensive analysis to better understand roles of the polymorphisms in skin cancer development among Caucasian population. The results showed that Fok1 polymorphism was associated with an overall significantly increased risk of skin cancer (Ff vs. FF: OR = 1.20, 95 % CI = 1.01–1.44; ff vs. FF: OR = 1.41, 95 % CI = 1.08–1.84; Ff + ff vs. FF: OR = 1.26, 95 % CI = 1.04–1.53). Besides, we found that Taq1 polymorphism could contribute to non-melanoma skin cancer susceptibility (Tt vs. TT: OR = 1.88, 95 % CI = 1.29–2.74; tt vs. TT: OR = 2.00, 95 % CI = 1.22–3.28; Tt + tt vs. TT: OR = 1.92, 95 % CI = 1.35–2.73). We also found that the Apa1 polymorphism is associated with skin cancer development (Aa vs. AA: OR = 1.27, 95 % CI = 1.05–1.53; Aa + aa vs. AA: OR = 1.23, 95 % CI = 1.04–1.47) and NMSC subgroup (Aa vs. AA: OR = 1.72, 95 % CI = 1.51–2.57; Aa + aa vs. AA: OR = 1.50, 95 % CI = 1.03–2.17). No significant association was observed between the Bsm1 polymorphism and skin cancer risk. The current meta-analysis shows that Fok1, Taq1 and Apa1 may be the susceptibility biomarker for skin cancer in Caucasians.