《会计学-企业决策的基础》.ppt

Genetic Variations in NER Pathway, Smoking and 11 Cancer Sites: a Pooled Study Yi Ren Wang Nucleotide Excision Repair Pathway DNA Damage and Repair Long-term effects of DNA damage may lead to irreversible mutations, contributing to oncogenesis Reduced DNA repair capacity may be related to an increased risk of cancers DNA Repair Base excision repair Nucleotide excision repair Mismatch repair Double-strand-break repair NER Pathway Particularly important mechanism by which the cell can prevent unwanted mutations by removing the vast majority of UV-induced DNA damage The primary mechanism for the repair of bulky and helical distorting DNA adducts generated by cigarette smoke Therefore, reduced efficiency of NER could increase susceptibility to DNA damage, and thus increase risk of cancer. NER Pathway Study Design Data Source Los Angeles Study: Lung: 611, UADT: 601 Controls: 1040 Memorial Sloan Kettering Cancer Center Study: Prostate: 154, Bladder: 245, Kidney: 34, Testes: 32 Controls: 205 TaiXing Study: Liver: 195, Esophagus: 205, Stomach: 196 Controls: 394 Study Design SAS 9.1 software was used for data analysis. ORs and 95% CLs was computed using unconditional logistic regression Potential confounding factors adjusted in pooled analysis: age, gender, ethnicity, tobacco smoking χ2 test is performed to evaluate Hardy-Weinberg equilibrium. 11 Cancer Sites Lung Oropharynx Nasopharynx Larynx Esophagus Bladder Kidney Liver Stomach Prostate Testes Established association with smoking Association with smoking unknown Candidate SNPs in NER Pathway Gene SNP Data Source Amino Acid Change XPC rs2229090 SNPlex ? XPC rs2470352 SNPlexTaqman ? XPD/ERCC2 rs238406 SNPlex R156R XPD/ERCC2 rs1052555 SNPlex D711D XPD/ERCC2 rs13181 SNPlex K751Q XPD/ERCC2 rs1799801 SNPlex S835S XPG/ERCC5 rs2227869 SNPlex C529S XPG/ERCC5 rs17655 SNPlex D1104H XPG/ERCC5 rs1047768 SNPlex H46H ERCC6 rs4253211 SNPlexTaqman R1230P ERCC6 rs2228529 SNPlexTaqman Q1413R ERCC1 rs