This study aimed to develop a LightCycler ( LC) assay to analyze the C>G polymorphism ( Ser326Cys)
in exon 7 of the hOGG1 gene followed by validation of the method using DNA samples from 260 polycyclic aromatic hydrocarbons( PAH)-exposed workers with known 8-oxodGuo DNA-adduct values measured by HPLC. Twenty DNA samples were analyzed by a PCR-RFLP analysis with Fnu4H I to generate HSP990 in vitro control DNA. LC melting curve analyses of the hOGG1 exon 7 PCR product were characteristic of the probes hybridized to the non-mutated Ser-type ( CC) at 65 C, or to the Cys mutant ( GG) at 59 C. The distribution in the population of PAH-exposed workers ( N=260) was 58% ( CC), 38%( CG), and 4% ( GG). The minor G allele displayed a frequency of 23 %. The distribution of 8-oxodGuo adducts for the Ser326Cys variants of hOGG1 revealed geometric means ( GM) of 5.83 ( CC), 5.27 ( CG), and 6.53 ( GG) 8-oxodGuo adducts/10(6)dGuo. Corresponding GM values of current smokers were 5.7 ( CC), 5.6
( CG) and 7.0 ( GG) 8-oxodGuo adducts/10(6) dGuo. The analysis of the Ser326Cys polymorphism in 260 DNA samples with this new LC assay revealed that this method is reliable for high throughput analysis of this key IWR-1 order polymorphism in the hOGG1 gene.”
“Cigarette smoking is the most important risk factor for development of transitional cell carcinoma of the urinary bladder. The effect of polymorphisms of glutathione S-transferases M1 (GSTM1) and M3 (GSTM3) on the influence of cigarette smoking on urinary bladder carcinogenesis was investigated. In total, 293 bladder cancer patients from hospitals in Dortmund and Wittenberg as well as 176 patients without any malignancy from a Department of Surgery from Dortmund were genotyped for GSTM1 and GSTM3 according to standard
PCR/RFLP methods. Smoking habits were quantified by a standardized interview. out The proportion of GSTM1 negative cases was 63% in the entire bladder cancer cases group compared to 50% in controls. The GSTM3* A/*A genotype was 76% in cancer cases versus 74% in controls. Smokers and ex-smokers were overrepresented in bladder cancer cases. A significant association between smoking status and GSTM1 or GSTM3 genotype was not detected. The elevated proportion of GSTM1 negative bladder cancer cases shows an effect of this polymorphic enzyme on development of bladder cancer. In contrast to other studies, an influence of GSTM1 on the risk due to cigarette smoking was not observed.”
“Tobacco smoking, alcohol drinking, and occupational exposures to polycyclic aromatic hydrocarbons are the major proven risk factors for human head and neck squamous-cell cancer ( HNSCC). Major research focus on gene-environment interactions concerning HNSCC has been on genes encoding enzymes of metabolism for tobacco smoke constituents and repair enzymes.