Font Size: a A A

Association Of XRCC1 Genetic Polymorphisms And Environmental Factors With The Susceptibility To Non-small Cell Lung Cancer

Posted on:2017-02-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:S R KangFull Text:PDF
GTID:1224330488480532Subject:Surgery
Abstract/Summary:PDF Full Text Request
Backgrounds and Objective:Lung cancer, lung cancer) is a worldwide in recent centuries malignant tumour of the highest rates About 1.8 million people with cancer, about accounted for 12.9% of the population mortality rates, about 58% of all cancer patients was concentrated in the developed countries in our country, the incidence of lung cancer among men in China in the first, ranked second for the incidence of female lung cancer incidence of a disease with the developed countries gradually decline trend is different, in recent years, the incidence is increasing in our country. Because our country is in the industrialization and urbanization development stage, such as air pollution, and could effectively control factors, morbidity and mortality of lung cancer is still in a rising trend According to China’s national cancer registry data show that in 2008 China’s newly diagnosed lung cancer cases for 522,050 people,2010 rose to 605,946. With the development of modern medical technology, many cancer such as gastric cancer cervical cancer mortality is declining, but the prognosis of lung cancer is very poor,5 years of survival rate is less than 20% of lung cancer mortality in China also first, according to statistics, in 2012, the mortality of lung cancer is 29.5/105.80-85% of the total number of lung cancer, non-small lung cancer mechanism of non-small cell lung cancer treatment as well as other tumors, the function and way of life by a variety of environmental factors lead to, and development is composed of multiple factors caused many gene for a long time and many steps According to the WHO estimates that each year about 1.8 million cancer is caused by smoking, more than 70% of lung cancer are caused by smoking Although most are made in patients with lung cancer have long-term smoking exposure history, but not all smokers get lung cancer, illustrates the other environmental factors and genetic factors and the risk factors of lung cancer By adopting a case-control study method, this study for subjects with non-small cell lung cancer information on common environmental factors, to explore influences of these factors in the pathogenesis, control of hybrid genetic factors for further analysis Understand the genetic environment interaction effects, the mechanism of non-small cell lung cancer take place as well as other tumors, the function and way of life by a variety of environmental factors lead to the different response to environmental factors exist differences between individuals, these differences are determined by genetic factors, single nucleotide polymorphism, single nucleotide polymorphisms, SNPs) which lead to lung cancer in different individuals susceptibility of one of the important reasons. Humans about 15 million SNPS loci, including an average of 300-600 bp is a base mutation of some functional SNPS in transcription way, can affect the body product or change in the number of the gene expression, making gene expression is different between different individuals, show the differences of genetic characteristics Therefore affect individual susceptibility to environmental risk factors, by detecting coding specific biomarkers of SNPs, are able to further clarify non-small cell lung cancer pathogenesis and susceptibility to provide the reference for environmental factors.Application of PCR-RFLP method, XRCC1 Arg399Gln, Arg194Trp and Arg280His these three loci were tested, the study found that XRCC1 Arg399Gln and Arg194Trp gene polymorphism and susceptibility to non-small cell lung cancer risk.Methods:In January 2012 to July 2014, in Inner Mongolia medical university affiliated hospital for surgical treatment of primary non-small cell lung cancer patients and in Inner Mongolia medical university affiliated hospital to undergo a medical healthy individuals According to the inclusion criteria and exclusion criteria included 244 case subjects and 268 controls. Non-small cell lung cancer risk factors for using self-designed questionnaire, by trained investigators in Inner Mongolia medical university affiliated hospital of the main content of the face to face questionnaire survey, including general demographic characteristics of study subjects, smoking exposure, indoor and outdoor air pollution exposure, drinking, dietary habits and height, and weight. By face to face questionnaire survey information collection, Epidata3.0 is adopted to establish the unified database, adopts the method of double entry of alignment error correction, to check the result of the entry. Using SPSS 19.0 (version 19.0, SPSS Inc., Chicago, IL, USA) statistical analysis, and extract the respondents peripheral venous blood of 5 ml, using ethylenediamine tetraacetic acid dipotassium antithrombotic treatment (EDTA-K2), put in-20 cryogenic refrigerator preservation under test will EDTA-K2 anticoagulation in acquisition of peripheral venous blood vessels 5 ml, according to the genome of blood extraction kit (QIAGEN GmbH) steps for the extraction of blood samples from the genome. XRCCl Arg399Gln Argl94Trp and Arg280His gene polymorphism detection using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method XRCCl Arg194Trp Arg280His and Arg399Gln three loci alleles of amplification products with PvuⅡ restriction endonucleases, Rsal restriction endonucleases and Mspl restriction endonuclease enzyme digestion. After the reaction, a product will take 5 mu 1 enzyme and 1 mu 1 bromophenol blue on the sample buffer blending for preliminary analysis, placed on a 3%agarose gel electrophoresis, and observed under uv light, all the statistical tests are bilateral inspection, and a less than 0.05 was considered significant difference.Results:The study into the investigation case group and the control group there was no statistically significant difference of gender and age, the age (x2=2.34, P=0.310) and gender(x2=0.43,p=0.513) distribution in equilibrium between the two groups found that BMI than chi-square where passive smoking fruits eggs have correlation with non-small cell lung cancer.Single factor analysis found that high BMI of patients with non-small cell lung cancer with weak correlation between BMI> 24 kg/m2 increases the risk of non-small cell lung cancer (OR= 1.46,95% CI= 1.012.13) live in rural individuals, the risk of non-small cell lung cancer is to live for the city’s individual 3.23 times (OR = 3.23,95% CI= 2.254.64). Have always smoking history of individual and individual, has a history of smoking compared with nonsmokers, non-small cell lung cancer risk increased 5.09 times and 7.29 times, corresponding the OR (95% CI) were 5.09 (3.05 8.51) and 7.29 (4.48 11.88) has a history of passive individuals and than individuals without passive smokers, a 1.67-fold increased risk of non-small cell lung cancer, corresponding the OR was 1.67 (95% CI) (1.142.45).Multiple factors regression analysis found that BMI> individuals with BMI< 24 kg/m2, compared to 18.5 kg/m2 of individual can increase the risk of non-small cell lung cancer, and the response OR(95%CI) was 1.63 (1.02-2.59). To live in rural, compared to individual and residence of the city’s individual risk of non-small cell lung cancer is 3.16 times (OR=3.16,95%CI=2.04-4.90) more than the individuals living in the city. Has a history of smoking individual and individual, has a history of smoking compared with nonsmokers, non-small cell lung cancer risk increased 8.83 times (OR=8.83,95%CI=5.02-15.54) and 6.68 times (OR=6.68,95%CI=3.69-12.08). Having a history of passive individuals compared with than individuals without passive smokers, a 1.90-fold increased risk of non-small cell lung cancer (OR=1.90, 95CI=1.18-3.06). Small amounts of alcohol and excessive drinking of individuals and not drinking, compared to the individual risk of non-small cell lung cancer has increased 2.51 times and 2.89 times, corresponding the OR (95% CI) were 2.51 (1.12-5.61) and 2.89 (1.26-6.65), respectively. Comparing appropriate eat eggs to those with too little to eat eggs, there was only 0.44 times the risk of non-small cell lung cancer, and corresponding the OR was 0.44 (95% CI=0.19-0.97).Using a goodness-of-fit chi square test, inspection, found that XRCC1 Arg194Trp (chi-square= 4.19, P= 4.19) Arg280His (chi-square= 5.65, P= 5.65) and Arg399Gln (chi-square= 12.52, P= 12.52) gene polymorphism frequencies do not conform to the Hardy Weinberg equilibrium distribution.XRCC1 Arg194Trp (chi-square= 12.68, P= 0.002) and XRCC1 Arg280His (chi-square= 12.29, P= 12.29) genetic gene frequency distribution in the case group and the control group was statistically significant.Multivariable logistic regression analysis found that the XRCC1 Arg194Trp, in co-dominant model, carrying Arg/Trp and Trp/Trp genotypes of individual risk of non-small cell lung cancer significantly higher than carry Arg/Arg genotype individuals, corresponding the OR value of 3.43 (95% CI) (1.577.51) and 2.67 (1.21 5.88) in the dominant model, carrying Arg/Trp+Trp/Trp genotypes of individual risk of non-small cell lung cancer is to carry Arg/Arg genotype individual 1.51 times (OR = 1.512.25) in recessive models, carrying the Trp/Trp genotypes of individual risk of non-small cell lung cancer is to carry Arg/Arg+3.00 times of Trp/Arg genotype individuals (OR= 3.00,95% CI= 1.426.36).Of XRCC1 Arg280His in co-dominant model, carrying Arg/ihs and the ihs/ihs genotype individuals and carry Arg/Arg genotype, compared to the individual risk of non-small cell lung cancer has increased 3.26 (OR= 3.26,95% CI= 1.387.73) and 2.84 (OR= 2.84,95% CI= 1.20 6.73) times in recessive models, carrying His/His genotype individuals and carry Arg/Arg+Arg/His genotypes, compared to the individual risk of non-small cell lung cancer has increased 2.96 times, corresponding the OR value of 2.96 (95% CI) (1.296.81) and in the dominant model, XRCC1 Arg280His gene polymorphism with no correlation between non-small cell lung cancer risk.In co-dominant, dominant and recessive models, the multi-factor logistic regression analysis found no XRCC1 Arg399Gln gene polymorphism and the risk of non-small cell lung cancer in the correlation (P> 0.05).Using Spearman correlation analysis, the study found that XRCC1 Arg194Trp and Arg280His gene polymorphism and BMI, where passive smoking drinking and eating eggs and no correlation between, explain XRCC1 Arg194Trp and Arg280His gene polymorphism are independent small cell lung cancer risk factors.Conclusion:Used single factor unconditioned logistic regression analysis found that BMI where smoking and passive smoking are the influence factors of small cell lung cancer. After further by multi-factor unconditioned logistic regression analysis found that, BMI, where passive smoking drinking and eggs are the influence factors of small cell lung cancer. Conclusion suggests that the future should be according to the relevant environmental factor to carry out preventive interventions, change bad habits such as smoking drinking, enhance nutrition and lower bmi increase weight appropriately, so as to effectively prevent the risk of non-small cell lung cancer. Using Spearman correlation analysis, the study found that XRCC1 Arg194Trp and Arg280His gene polymorphism and BMI, where passive smoking drinking and eating eggs and no correlation between, explain XRCC1 Arg194Trp and Arg280His gene polymorphism are independent small cell lung cancer risk factors.
Keywords/Search Tags:non-small cell lung cancer, Environmental risk factors, XRCC1, Arg194Trp, Arg280His, Arg399Gln, Genetic polymorphism, Cancer risk
PDF Full Text Request
Related items