| Analysis of p53 and Retinoblasoma(Rb) Gene Polymorphisms in Relation to Lung Cancer in Koreans. |
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Kyung Sang Lee, Jang Won Sohn, Suck Chul Yang, Ho Joo Yoon, Dong Ho Shin, Sung Soo Park, Jung Hee Lee, Chun Geun Lee, Youl Hee Cho |
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| Abstract |
BACKGROUND
The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial. proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. METHODS: In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis The two intragenic polymorphisms of the p53 gene(exon 4/AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain react lion-restriction fragment length polymorphisms(PCR-RFLPS). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. RESULTS: There were no significant differences in the genotype distributions of the p53 gene between lung cart cert patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AcclII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known 13 be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p=0.0297) or adenocarcinomas(p=0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were a]so noted between the high dose smokers and low dose smokers including non-smokers(p=0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio=0.46, 95%C.I.=0.25-0.86, p=0.0124). The combined genotype distribution of the exon 4/AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/pro and r2/r2(odds ratio=1.97, 95%C.I.=0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio=0.54, 95%C.I.=0.25-1.14). CONCLUSION: The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koreans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed. |
| Key Words:
p53 & retinoblastoma gene polymorphism, Lung cancer |
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