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Gene polymorphisms of the DNA Repairing Genes APE1 and XRCC1 among Smoking Lung Cancer Egyptians

Keywords: Gene , polymorphisms , DNA Repairing Genes , APE1 , XRCC1 , Lung Cancer

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Abstract:

Lung cancer is the leading cause of cancer-related mortality worldwide and is thus a major public health problem. DNA base damage or losses caused by endogenous and exogenous agents occur constantly at a high frequency in human cells. The removal or repair of damaged bases is an important mechanism in protecting the integrity of the genome. APE1 (Apurinic/Apyrimidinic Endonuclease 1) and XRCC1 (X-ray cross-complementing group1) are DNA repair proteins that play important roles in the base excision repair (BER) pathway. The focus of this work is limited to the association between polymorphisms in the DNA repair genes, (APE1 Asp148Glu (2197 T→G) and XRCC1 Arg399Gln (28152 G→A) genotypes), cigarette smoking and lung cancer. This study has included 131 cases affected with lung cancers include; 33cases with small cell carcinoma (25.2%) and 98 cases with non-small cell carcinoma (74.8%). They were recruited from oncology Center, Mansoura University, Egypt; in the period between April 2008 to March 2010. For comparison, a negative control group including 150 healthy individuals randomly selected from blood donors. Controls were selected by random sampling cancer-free individuals without a past history of cancer, who visited Mansoura University hospitals and provided peripheral blood between April 2008 and March 2010. DNA was extracted from the whole peripheral blood using generation DNA purification capture column kit (Gentra system, USA) and genotyping for APE1 Glu148Asp and XRCC1 Arg399Gln polymorphisms was performed by a PCR--CTPP (PCR with confronting two-pair primers) method. The collected data were organized and statistically analyzed using SPSS statistical computer package version 10 software. we observed that, There were no significant differences in the frequencies of the APE1 Asp148Glu (2197 T→G) polymorphism of all genotypes and alleles in all lung cancer cases compared to all healthy controls. Also, there were no significant differences in the frequencies of all genotypes and alleles in lung cancer cases compared to controls of all smoking status. While, in former smoking individuals; significant difference in the frequency of the mutant GG genotype in lung cancer cases compared to controls (p-value=0.003). We observed that, There were no significant differences in the frequencies of the XRCC1 Arg399Gln (28152 G→A) polymorphism of all genotypes and alleles in all lung cancer cases compared to all healthy controls. Also, there were no significant differences in the frequencies of all genotypes and alleles in lung cancer cases compared to controls of

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