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Molecular Epidemiology Study on MiRNA Region Polymorphisms and the Susceptibility and Survival of Lung

Author: TianTian
Tutor: ShenHongBing
School: Nanjing Medical University
Course: Epidemiology and Biostatistics,
Keywords: Lung cancer miRNAs Single nucleotide polymorphisms Case - control study Genetic predisposition Prognosis
CLC: R734.2
Type: Master's thesis
Year: 2009
Downloads: 144
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Abstract

Lung cancer is one of the most common in the world and the highest mortality rate of malignant tumors, and many cities in many countries, and China has been ranked first of all cancer cause of death. In the past few decades, China's population of lung cancer incidence and mortality in the rapid growth of more than the world's average level, and has continued to show a rising trend, becoming one of the major public health threat to the health of our residents. These protein-coding genes in the exploration lung cancer development and prognosis of the process, a large number of molecular epidemiological studies have shown that there are hundreds of protein-coding genes involved in the occurrence and development of lung cancer, such as p53, Rb, Ras lung cancer susceptibility and prognosis play an important role. In recent years, non-protein-coding RNAs in malignant tumors (including lung cancer) occurs role in the development of more and more concern for people. MicroRNAs (miRNAs) are a class size of about 21-24 nucleotides (nucleotide, nt), non-coding RNAs, which pairing with target mRNAs 3'-untranslated region (untranslated region, UTR) nucleotide regulatory genes The expression, can lead to the inhibition of the degradation of the target mRNA or translation. MiRNA regulation disorders (including change of expression), the impact of the target mRNA transcription regulation, can participate in almost all of the pathophysiological process. In addition, a single miRNA can regulate hundreds of different functions of target mRNAs and miRNAs expected to become a new class of important tumor susceptibility gene. Therefore, this subject miRNAs as representatives of non-protein-coding gene molecular epidemiological studies of miRNAs regions of the genome variation and lung cancer susceptibility and prognosis. Single nucleotide polymorphisms (single nucleotide polymorphism, SNP) is the most common human genetic alterations, a large number of epidemiological studies have shown that the SNP changes can affect tumors (including lung cancer) occurred development and prognosis. With miRNA is representative of a large class of non-protein-coding RNA discovery, finding SNPs associated with lung cancer susceptibility and prognosis miRNAs within the regions of the genome research will open up a new way to explore the pathogenesis of lung cancer and other. In this study, we miRBase public database (http://microrna.sanger.ac.uk/targets/) as a basis for screening out the need for research SNPs in case - control study design to explore miRNAs gene region polymorphism sexual change the association between individual genetic susceptibility of lung cancer, prospective study designed to explore the association between miRNAs gene region polymorphisms and lung cancer prognosis, research results can be more reasonable for the development of lung cancer prevention and treatment strategies and individualized treatment The programs provide clues. The first part of miRNAs gene region polymorphism and lung cancer prognosis prospective study of this study successful follow-up, including a total of 663 cases of lung cancer cases, to investigate miRNAs gene region polymorphisms change the association between lung cancer prognosis. Due to the SNP mutation essence, our research hypothesis: changes may affect miRNAs expression levels and prognosis of lung cancer associated miRNAs and near the area of ??the SNPs. To verify the hypothesis, we first miRBase public database of 400 known miRNAs and its nearby area of ??common SNPs (minor allele frequency, MAF gt; 0.05) Screening of the system, and finally select is located has-miR-146a , has-miR-149, has-miR-196a2 and has-miR-499 precursor miRNAs gene region on four Chinese populations common SNPs sites (for rs2910164, rs2292832, rs11614913, rs3746444), carried out in two stages ( two-stage) follow-up study of non-small cell lung cancer prognosis. The results showed that carrying miR-196a2 3p regions of the genome loci the rs11614913 mutation homozygous CC genotype carrying CT / TT genotype compared mortality risk was significantly increased by 76% (HR = 1.76, 95% CI = 1.34-2.33), death to advance 5.9. Analysis of the lung tissue sample genotype - phenotype, rs11614913 CC mutation homozygous and mature miR-196a expression is related to the rise, but does not give rise to the increase in the expression of the precursor, suggesting that miR-change in the polymorphic sites 196a of the maturation process is limited. The present study demonstrates located in miR-196a2 3p rs11614913 polymorphism loci may affect mature miR-196a expression associated with the prognosis of lung cancer, suggesting that we located the the polymorphism changes may miRNAs gene region on lung cancer prognosis forecasting and lung cancer individualized treatment provides new clues. The second part of miRNAs gene region polymorphisms and susceptibility to lung cancer case - control study of this study includes a total of 1058 cases of new hair histopathologic diagnosis of lung cancer cases and 1,035 cases frequency matched by sex and age, with the case group community controls crowd. Our assumption is: SNPs change may affect miRNAs expression levels of genetic susceptibility of lung cancer associated miRNAs gene and its surrounding area. To verify that hypothesis, we have screened for the current in the has-miR-146a, has-miR-149, has-miR-196a2 and has-miR-499 precursor miRNAs gene region on four Chinese crowd SNPs (rs2910164, rs2292832, rs11614913, rs3746444), conducted a large sample of lung cancer genetic susceptibility case - control study. The unit point Logistic regression analysis showed that, adjusted for sex, age, cumulative smoking factors recessive genetic model CC genotype (homozygous mutant with two genotypes CT / TT compared), located miR change and the risk of lung cancer was significantly related rs11614913 polymorphism-196a2 3p gene region, carrying miR-196a2 rs11614913 CC genotype increased risk of lung cancer by 25% (adjusted OR = 1.25, 95% CI = 1.01 -1.54). However, the study did not observe a main effect to other sites on the risk of lung cancer. Genotype - phenotype analysis results in the first part of the study, the results of this study suggest that miR-196a2 3p gene region rs11614913 polymorphism change may affect the genetic susceptibility of lung cancer by changing the expression of mature miR-196a , the result has some significance for early lung cancer screening and prevention.

Molecular Epidemiology Study on MiRNA Region Polymorphisms and the Susceptibility and Survival of Lung

Abstract

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