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Single-nucleotide Polymorphisms In VTI1A Gene Contribute To The Susceptibility Of Chinese Population To Non-small-cell Lung Cancer

Posted on:2016-11-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:W M SuFull Text:PDF
GTID:1224330482956583Subject:Oncology
Abstract/Summary:PDF Full Text Request
BackgroundLung cancer is one of the most common malignant tumors in the world. In China, men and women both have a high mortality rate due to lung cancer. And in recent decades, the 5-year survival rate of lung cancer is only about 15%, which has not improved much. According to the released material from our tumor prevention office, it showed that since the 1970s, the mortality of lung cancer in China rose by nearly 5 times as much. Lung cancer, one of the main diseases of residents’lives and health, has become a serious issue to our country. Epidemiological research results show that the occurrence of lung cancer is associated with genetic factors and environmental factors at the same time, and a lot of research shows that about 80% of lung cancer can be attributed to the tobacco exposure, and the incidence of smokers getting lung cancer is nearly 10 times higher than that of nonsmokers. But not all smoking patients suffer from lung cancer. The occurrence of lung cancer may be related to other factors, including gene polymorphism variation, which may be a risk factor for the pathogenesis of lung cancer. With the development of lung cancer epidemiology and advancement of lung cancer research, the level of molecular biology in non-small cell lung cancer genetic research also becomes more and more developed.With the promoting of the international project aimed at developing a haplotype map of the human genome and the completion of the human genome project, in addition the establishment and improvement of the platform for high-throughput technology, Genome-wide Association Studies (GWAS) provides a powerful tool for the study of genetic susceptibility in complex diseases such as lung cancer. The basic principle of GWAS is as follows:within the target population, the case and control group are defined and the difference of allele or genotype frequencies on all single nucleotide polymorphism (SNP) within the scope of whole-genome between the two groups are compared. If the allele or genotype frequency on a SNP in case group is apparently higher or lower comparing with the control group, there is a relationship between this locus and disease. Then according to the location of the locus in the genome and linkage disequilibrium relationships, the potential disease susceptibility gene is presumed. Currently, GWAS has screened a number of common genetic variants associated with genetic susceptibility to lung cancer, in which the genetic variation located in 5p15,6p21 and 10q25.2 chromosome sections are involved in regulating nicotine acetylcholine receptor genes and generating telomerase genes, thus they are closely related to the developing of lung cancer. These findings suggested that it might contribute to the etiology study of lung cancer and the screening of high-risk populations with lung cancer by detecting genetic molecular markers associated with developing lung cancer.Gene polymorphism refers to the existence of two or more discrete alleles, variant, or genotypes at the same time in a biological group. According to the order of gene polymorphism research, gene polymorphism can be divided into three categories, single nucleotide polymorphisms (SNP), the repetitive sequence of DNA polymorphism (RSP) and restriction fragment length polymorphism (RFLP), respectively. These three kinds of gene polymorphism can reflect difference in individual hereditary susceptibility, for the genetic correlation research and clinical diagnosis of the disease. SNP (single nucleotide polymorphism) is the most common of human variation genetics. Single nucleotide C, G, A or T change and form the gene polymorphism, which accounts for more than 90% of all known polymorphism variations. SNP in the human genome is widespread, on average one in every 500-1000 base pairs is a polymorphism variation. It is estimated it could be 3 million or more in total. SNP is easy to operate on due to the high density, good stability and parting the advantages of the test, which still play an important role in terms of genetic disease gene identification. There are research results that was published in Nature journal 2012, which tell us the genome-wide association studies (Genome-wide association studies, GWAS) may have found a new SNP loci, namely VTI1A (rs7086803). It can cause an increase in the Asian nonsmoking women patients with lung cancer risk. There is currently no further research of the gene loci in world.Currently, it is a key topic in the field of lung cancer study to investigate the relationship between SNP and lung cancer susceptibility. And investigators have screened some chromosomal regions associated with susceptibility to lung cancer. For example, the independent studies from France, Iceland and the United Kingdom in 2008 demonstrated, through the GWAS analysis in lung cancer patients and healthy population, the changes of SNPs are associated with the developing of lung cancer. The results of this studies showed that genetic factors also play a key role in the pathogenesis of lung cancer. In studies from U.S. MD Anderson Cancer Center, Amos et al. detected 315,450 SNPs in smoking non-small cell lung cancer (NSCLC) patients and 1,137 healthy people which were matched with respect to smoking status. The results showed that the incidence of lung cancer is closely related with 10 SNPs, rs8034191、rsl2956651 and rs855974, respectively. Afterwards, further studies were conducted and concluded that the distribution of SNPs varies in different ethnic populations. For example, European GWAS demonstrated that the SNPs of rsl6969968、rs1051730 and rs8034191 located on chromosome 15q25.1 region were significantly associated with lung cancer in smokers and non-smokers. However, studies in South Korean, Japanese and Chinese populations have failed to repeat the experimental findings. The reason may be attributed to the lower frequencies of these polymorphic loci in Asian populations. These studies suggested that lung cancer susceptibility loci may vary in different ethnic populations. In our country, the risk of female lung cancer patients, without smoking, is not uncommon. But existing research shows that part of the non-smoking female lung cancer patients have special phenotypes such as EGFR mutations, ALK rearrangement, cMET amplification, etc. These results suggest that non-smoking women with the mechanism for lung cancer may overlap with smokers of lung cancer at the same time, and with its unique molecular pathways. As a result, non-smoking female of Asian with the 10 q25 rs7086803 loci area has a higher risk of lung cancer than that of smoking females, and how’s the mechanism of the polymorphic loci distribution in China’s overall population. All these factors require us to further explore and research.Adiponectin (ADIPOQ), is specificity secreted by white adipose tissue, then secreted into the blood circulation, insulin sensitization and resistance against atherosclerosis and diabetes, plays a powerful physiological regulator.To explore the relationship between adiponectin levels and lung cancer, Petridou conducted a clinical case-control study of 85 casesAccording to the results of the study, serum adiponectin level of lung cancer patients is not significantly different between the case groups and control groups. Another study is to explore the relationship between insulin resistance (Insulinresistance) and lung cancer. This study by Petridou etc also got similar results. But Petridou etc. showed the results that serum adiponectin level of patients, with advanced lung cancer, is significantly lower than the patients with limited lung cancer (odds ratio:0.25,95% CI:0.10-0.78), and further found that the expression of adiponectin receptors (AdipoR) is in the cancer tissue, but not in the normal lung tissues. He did this byusing immunohistochemical analysis. AdipoRl shows up in all types of lung cancer, and there is no difference in the different stages. And AdipoR2 mainly expresses in small cell lung cancer and advanced non-small cell lung cancer. Epidemiological investigation and research results show that fat factor in the relation between obesity and cancer plays a very important role in their morbidity and mortality rate such as in breast cancer, endometrial cancer, colon cancer and prostate cancer. Many studies in vitro suggests that certain fat factor may be associated with the growth of different cancer cell lines, moreover, some clinical research studies report the fat factor is in correlation with cancer susceptibility, pathologic types and prognosis in different types of cancer. In the past, the study suggests fat factor may be one of the high risk factors of lung cancer. Clinical data analysis showed that obesity can reduce the mortality of lung cancer (not factoring in smoking status), and can prolong the survival of patients.The proteins are secreted by fat cells containing VTI1A follicular. If VTI1A decrease in fat cells, then protein secretion is even less. Low yield of fat proteins are associated with the development of lung cancer. Whether VTI1A can affect the susceptibility of lung cancer through adiponectin remains to be further studied as well as the exact mechanism relationship between VTI1A and adiponectin receptor. It is very significance and necessary in regards to making sure treatment of lung cancer, as well as understandingthe development that VTI1A and adiponectin receptor play in lung cancer.This study aims to discuss the relationship between gene polymoiphism in chromosome 10q25.2, the incidence of lung cancer and relation with AdipoR in the Chinese population. Through the case-control analysis, providing theoretical basis and a data base for screening early diagnosis and individualized treatment in high-risk lung cancer populations is possible. The subjects of study are limited to the Chinese population with lung cancer. The pathological type of cases will be re-classified in accordance with international multidisciplinary classification of lung cancer. Roche Light Cycler 480 System Ⅱ was used to determine genotyping in the Chinese lung cancer patients as well as the healthy control subjects. On one hand, the statistical analysis of each locus polymorphism and its relationship with lung cancer susceptibility was conducted to identify lung cancer susceptibility VTI1A (rs7086803) SNP suitable for the China population. And on the other hand, the stratified analysis of relationship between each locus polymorphism and gender, smoking status, histological type and TNM clinical stage in patients with lung cancer was also conducted to explore the association between genotype distribution and clinicopathological factors. Inimunohistochemistry was used to detect the expression level of AdipoRl protein on positive loci in lung cancer tissues, and to further validate the role of this gene in development of lung cancer. Based on this data, the preliminary data base and tiieoretical basis would be established for identifying and individualizing prevention and treatment of lung adenocarcinoma in high-risk populations in southern China, and it would also be prepared for the next step to establish a risk assessment model of lung adenocarcinoma susceptibility gene for southern Chinese populations.Chapter 1 Detect VTI1A (rs7086803) SNP in non-small cell lung cancer and expression of the general population in ChinaObjectDetect VTI1A non-small cell lung cancer and normal people in China the expression frequency (including men, women; smoking and non-smoking) in lung cancer patients and normal people, and verify whether VTI1A gene polymorphism frequency is the specificity susceptibility genes of the female patients with non-small cell lung cancer.MethodA consecutive group of 887 patients newly diagnosed with the TNM stage IV non small cell lung cancer at Guangdong Lung Cancer Institute (GLCI) between March 1998 and March 2012 were enrolled in this retrospective analysis. All the patients had provided consent for the use of their tumor samples for molecular and pathological analyses. Normal people in the control groups, patients with non-small cell lung cancer for the observation group. Collected blood samples and extracted DNA. Then used the Taqman probe method to test the gene polymorphisms, test site for VTI1A (rs7086803), after DNA amplification, PCR fluorescent signal collection, according to the fluorescence signal to map the genotype distribution of scatter diagram, sand then analys VTI1A (rs7086803) genotype distribution. All analyses were performed using SPSS 13.0 software. The chi-square test was used to compare qualitative variables, and those with an expected frequency of< 5 were analyzed by Fisher’s exact test. A two-sided P-value of<0.05 was defined as statistically significant.Results1) Hardy Weinberg equilibrium test We can find that patients with normal persons in different VTI1A (rs7086803) SNP genotype distribution of polymorphism loci which difference was not statistically significant using the goodness-of-fit chi-square test (P> 0.05), and according with Hardy-Weinberg, this article choose representative samples which have the very good specific data.2) From March 1998 to March 2012, we had the group of 887 patients diagnosed with non-small cell lung cancer and got the patients clinical information in detail. There was healthy people the as control group. Patients with lung cancer were the observation group. In non-small cell lung cancer group, there were 228 cases of male patients (30.6%), and 518 cases of female patients (69.4%); Patient’s age ranged from 27-86 years old. The the median age was 60 years old; Smoking status:smoking for 159 cases (21.3%) patients,587 cases (78.7%). The normal group comprised of male patients with 25 cases (17.7%), and 116 cases of female patients (82.3%). Patient’s age ranged from 15-78 years old, the median age was 42 years old; Smoking status: smoking for 14 cases (9.9%) patients,127 cases (90.1%).3) In non-small cell lung cancer group there was 746 cases, we analyzed the VTI1A (rs7086803) genotype frequency relationship with the clinical pathological features. VTI1A (rs7086803) SNP was divided into three groups, respectively AA, AG, GG group. Each group was divided into two groups, each with different clinical pathological features and we found that the gene loci and gender, age, tumor pathologic type, lymph node metastasis, distant metastasis, TNM stage, smoking status, treatment were not statistically significant. But this likely is related to our small sample size.4) We choose two groups. One was the observation group for non-small cell lung cancer 746 examples, and the another control group was a normal populations group of 141 cases. We analyzed VTI1A (rs7086803) genotype frequency in the case of the expression rate in the two groups. Genetic state can be divided into three groups, one group of GG, AG, AA; a group of AG + GG, AA, a set of AG + AA, GG. In the first group, the observation group of GG accounted for 45.4%, AG 42.5%, AA (12.1%); In the control group, GG 57.4%, AG 32.6%, AA (10%); Constituent ratios of this three types its chi-square was 6.893, P= 0.032, the difference was statistically significant. GG genotype as the reference, AG vs. GG:OR= 1.647,95% CI= 1.112-2.439, P= 0.007; AA vs. GG:OR= 1.536,95% CI-0.832-2.836, P= 0.168; In the second group, in observation group AG + GG(87.9%), AA (12.1%); In the control group, AG +GG accounted for 90.0%, AA (10.0%); Constituent ratios of the two types its chi-square was 0.522, P= 0.470. Using AG+GG genotype as the reference, AA vs. AG+GG:OR= 1.245,95% CI= 0.687 2.255, P= 0.470; In the third group, AG+ AA accounted for 54.6%, GG accounted for 45.4% in observation group; In the control group, AG+AA accounted for 42.6%, GG accounted for 57.4%; Constituent ratios of the two types of chi-square was 6.866, P= 0.009. Using AG + AA genotype as the reference, AG+AA vs. GG:OR= 1.621,95% CI= 1.127-2.335, P= 0.009. The data shows the variable GG genotype great correlation with the susceptibility of lung cancer.5) Basing on gender stratification factor, we observed VTI1A (rs7086803) gene frequencies of different expressions in female lung cancer patients and the normal population. We incorporated two groups; one group the observation group,518 cases for female patients with lung cancer, and a set of control group,126 cases of female normal population. Genetic state can be divided into three groups, one group of GG AG, AA; a group of AG + GQ AA, a set of AG + AA, GG. In the first group, the observation group of GG accounted for 43.8%, AG 43.2%, AA (13.0%); In the control group, GG 60.3%, AG 32.8%, AA (6.9%); Constituent ratios of this three types its chi-square was 10.965, P= 0.004). Using GG genotype as the reference, AG vs. GG:OR=1.818,95% CI= 1.175-2.811, P= 0.007; AA vs. GG:OR= 2.583,95% CI= 1.183-5.637; P= 0.014; In the second group, in observation group, AG + GG(87.1%),AA(12.9%);In the control group,AG+GG accounted for 93.1%,AA (6.9%);Constituent ratios of the two groups of chi-square was 4.271,P = 0.039). Using AG+GG genotype as the reference,AA vs.AG + GG:OR:2.191,95% CI= 1.024-4.689,P=0.039;In the third group,in observation group,AG + AA accounted for 56.2%,GG accounted for 43.8%;In the control group,AG + AA accounted for 39.7%,GG accounted for 60.3%;Constituent ratios of the two groups of chi-square was 10.391,P=0.001.Using AG + AA genotype as the reference,AG + AA vs.GG: OR=1.951,95% CI=1.294-2.941,P=0.001.Therefore,VTI1A(rs7086803)A allele may be a cause of women suffering from lung cancer susceptibility genes.6)Based on gender stratification factors,we observed VTI1A(rs7086803)gene frequencies of different expression in male patients with lung cancer and normal people.We incorporated two groups,one group the observation group,228 cases of male patients with lung cancer,and a set of control group,25 cases for normal men. Genetic state can be divided into three groups,one group of GG, AG, AA;a group of AG + GG AA,a set of AG + AA,GG. In the first group,the observation group of GG accounted for 49.1%,AG 40.8%,AA(10.1%);In the control group,GG 44.0%,AG 32.0%,AA(24.0%);Constituent ratios of the two groups of chi-square was 4.362,P =0.113.Using GG genotype as the reference,AG vs.GG:OR:1.142,95% CI= 0.441-2.956; P=0.785;AA vs.GG:OR = 0.376,95% CI:0.126-1.121;P=0.071; In the second group,in observation group AG + GG(89.9%),AA(10.1%);In the control group,AG + GG accounted for 76.0%,AA(24.0%);Constituent ratios of the two groups of chi-square was 4.297,P=0.038.Using AG + GG genotype as the reference,AA vs.AG + GG:OR=0.355,95% CI=0.129-0.979; P=0.038;In the third group,in observation group AG + AA accounted for 50.9%,GG accounted for 49.1%;In the control group, AG + AA accounted for 56.0%,GG accounted for 44.0%; Constituent ratios of the two groups of chi-square was 0.237,P=0.627.Using AG + AA genotype as the reference, AG+AA vs. GG:OR= 0.814,95% CI= 0.654-1.869; P= 0.627. Therefore, VTI1A (rs7086803) of A allele may not protect men crowd is suffering from lung cancer gene, its role in contrast to the women.Conclusion1. We analyzed the correlations between the genotypes of rs7086803 polymorphism and the patients’clinical parameters, namely, age, gender, tumor subtype, lymph node metastasis, distant metastasis, TNM stage, and smoking status. No significant association between VTI1A (rs7086803) genotypes and clinical parameters was observed, although our test sample size was small。2. The rate of the allele A of VTI1A (rs7086803) in Chinese female lung cancer groups is higher than the normal women crowd.Chapter 2 The prognosis of the correlation between non-small cell lung cancer expression of VTI1A (rs7086803) SNP and the smoking statusObjectiveAnalyze the prognosis of non-small cell lung cancer patients in different smoking status for their different expression of VTI1A (rs7086803) SNP.MethodsA consecutive group of 734 patients newly diagnosed with the TNM stage IV non small cell lung cancer at Guangdong Lung Cancer Institute (GLCI) between March 1998 and March 2012 were enrolled in this retrospective analysis. All the patients had provided consent for the use of their tumor samples for molecular and pathological analyses.Patients’ clinical information and treatment was obtained from Guangdong province people’s hospital electronic medical record system query, and followed-up by telephone and outpatient interviews. Follow-up plan is for once every 12 weeks. For patients who failed to query to the relevant information in medical records system, a querywas done by telephone to follow-up on the patients’ overall survival (OS). Overall survival is defined as the time from diagnosis to the time of death. Deleted data loss is defined as the last follow-up time survival or patients lost to the follow-up. Smoking status was established, including smoking and non-smoking; no smoking is defined as patients who smoked fewer than 100 cigarettes in their lifetime. Smokers who smoked more than 100 cigarettes, defined as patients life involves past smoking has quit smoking, and smoke.Using SPSS 13.0 software for statistical analysis of experimental results with Kaplan Meier method for univariate survival analysis, analyze the comparison between the levels of various factors by the Log-rank method. Use the Cox proportional hazards model for multiple factors analysis. A two-sided P-value of <0.05 was defined as statistically significant.Results1. The comparison of AA, AG, GG three groups1) GG group 1,2,3 year survival rates were 78.0%,60.0%,45.4%, the median survival was 31.3 months. AG group 1,2,3 year survival rates were 73.9%,59.2%, 46.5%, the median survival was 32.2 months. AA group 1,2,3 year survival rates were 79.7%,48.3%,38.1%, the median survival was 22.2 months. Log-rank method, according to the results of three groups of survival there was no significant difference compared (X2=1.152, P=0.562).2) According to whether smoking or not, patients will be stratified. In smoking patients, to the end of the follow-up, GG group 1,2,3 year survival rates were 58.4%, 44.7%,34.6%, the median survival was 16.7 months. AG group 1,2,3 year survival rates were 64.1% ,50.2%,41.6%, the median survival was 26.4 months. AA group 1, 2 year survival rates were 16.7% ,8.3%, the median survival was 9.5 months. Log-rank method, according to the results of three groups of survival in patients with comparative differences are significant (X2=8.102, P=0.017), AA patients survival curve has an obvious downward trend.3) In the patients who are non-smokers, GG group 1,2,3 year survival rates were 83.3%,64.4%,47.7%, the median survival was 34.3 months. AG group 1,2,3 year survival rates were 76.7%,61.2%,48.0%, the median survival was 33.6 months. AA group 1,2,3 year survival rates were 86.1%,56.4%,44.5%, the median survival was 32.6 months. Log-rank method, according to the results of three groups of survival there was no significant difference compared (X2=0.337, P=0.835).2. Comparing the two groups of AA+AG, GG1) AA+AG group 1,2,3 year survival rates were 75.2%,57.1%,44.8%, the median survival was 31.7 months. GG group 1,2,3 year survival rates were 78.0%, 59.9%,45.4%, the median survival was 31.3 months. Log-rank method, according to the results of two groups there was no significant difference comparing survival of (X2=0.226, P=0.635).2) According to whether smoking or not, patients will be stratified. In smoking patients, to the end of the follow-up, AA+AG group 1,2,3 year survival rates were 60.1%,43.2%,35.9%, the median survival was 18.3 months. GG group 1,2,3 year survival rates were 58.4%,44.7%,34.6%, the median survival was 16.7 months. Log- rank method, according to the results there was no significant difference comparison of three groups of survival in patients with (X2=0.007, P=0.932).3) In the patients with non smoking, AA+AG group 1,2,3 year survival rates were 79.2%,60.4%,47.4%, the median survival was 32.9 months. GG group 1,2,3 year survival rates were 83.3%,64.4%,47.7%, the median survival was 34.3 months. Log-rank method, according to the results of three groups of survival there was no significant difference compared (x2=0.329, p=0.566).3. Comparing two groups of AA, AG+GG1) AA group 1,2,3 year survival rates were 79.7%,48.3%,38.1%, the median survival was 22.2 months. AG+GG group 1,2,3 year survival rates were 76.0%, 59.8%,46.1%, the median survival was 31.7 months. Log-rank method, according to the results of two groups there was no significant difference comparing survival of (x2=1.137, P=0.286).2) According to whether smoking or not, patients will be stratified. In smoking patients, to the end of the follow-up, AA patients 1,2 year survival rates were 41.7%, 8.3%, the median survival was 9.5 months. AG+GG group 1,2,3 year survival rates were was 61.2%,47.4%,37.6%, the median survival was 21.4 months. Log-rank method, according to the results of three groups of survival in patients with comparative differences was significant (x2=7.705, P=0.006), survival curve of AA group have significant downward trend.3) In the patients who are non-smokers, AA group 1,2,3 year survival rates were 86.1%,56.4%,44.5%, the median survival was 32.6 months. AG+GG group 1, 2,3 year survival rates were 80.1%,63.1%,48.0%, the median survival was 34.3 months. Log-rank method, according to the results of three groups of survival there was no significant difference compared (x2=0.079, P=0.748).4. Multi-factor analysisThe single factor analysis of risk of AA phenotypic which is statistically significant will be introduced into Cox proportional regression model analysis, to explore the prognostic factors of patients with lung cancer, at the same time also is introduced including gender, age, pathological type, lymph node metastasis, clinical stage, smoking status and other factors, the young older patients survival in patients is longer (HR= 1.013,95% CI:1.001-1.023), the survival of patients is relatively shorter with middle-late period than with early metaphase (HR= 5.433,95%CI: 4.233-6.972), the survival of patients is shorter with lymph node metastasis than without lymph node metastasis (HR=1.225,95%CI:1.094-1.371), the survival of patients is relatively shorter with smoking than non-smoking (HR= 1.701, 95%CI: 1.330-2.176). Combined with the above results, age, clinical stage, lymph node metastasis and smoking status are significantly associated with the prognosis of patients in lung cancer, which are independent prognostic factors in patients with lung cancer.Risk factors such as AA phenotype, gender, age, pathological type, lymph node metastasis, clinical stage respectively introducing into the Cox regression model analysis, to explore the prognostic factors of smoking and nonsmoking patients with lung cancer, the results showed that smoking with lung cancer patients, the survival of younger patients is longer than older in patients (HR= 1.025,95% CI:1.002-1.050); The survival of patients with lymph node metastasis is shorter than without lymph node metastasis (HR= 1.547,95% CI:1.173-2.041); The survival of patients with middle-late period is relatively shorter than early metaphase (HR= 5.410,95% CI: 3.056-9.578), the AA phenotype of patients survival is shorter than the non-AA phenotypes of patients (HR= 1.954,95% CI:1.037-3.684); Younger patients survival is longer than older patients in non-smokers with lung cancer (HR= 1.011,95% CI: 1.001-1.021); The survival of patients is shorter with lymph node metastasis than without lymph node metastasis (HR=1.175,95% CI:1.035-1.334); The survival of patients is relatively shorter with middle-late period than with early metaphase (HR= 5.189,95% CI:3.922-6.864). Combined with the above results, we can see that, age, lymph node metastasis, clinical stage and whether AA phenotype and smoking was significantly associated with the prognosis of patients with lung cancer. Smoking is an independent prognostic factor in patients with lung cancer; at the same time, age, lymph node metastasis and clinical stage and the non smoking is significantly associated with the prognosis of patients with lung cancer. Non-smoking is not an independent prognostic factor in patients with lung cancer.Conclusion1. Survival in lung cancer groups was not significantly different in the three groups of AA, AG, GG, but in smokers, the patients have significant survival difference comparison in three groups, survival curve of AA group have significant downward trend.2. AA+GG and AG of the two groups in the lung cancer group, stratified factors of smoking or not had no significant survival difference in the comparison.3. AA and AG+GG survival of lung cancer in people compared between two groups had no significant difference. But smoking in the crowd, there are significant difference comparison of three groups of survival in patients, survival curve of AA group have significant downward trend.4. Gender, age, lymph node metastasis and clinical stage are significantly associated with the prognosis of patients with lung cancer, which are independent prognostic factors in patients with lung cancer.5. Age, lymph node metastasis, clinical stage and whether AA phenotype and smoking was significantly associated with the prognosis of patients with lung cancer, smoking is independent prognostic factor in patients with lung cancer; At the same time, age, lymph node metastasis and clinical stage and the non smoking was significantly associated with the prognosis of patients with lung cancer, smoking is not an independent prognostic factor in patients with lung cancer.Chapter 3 The research of VTI1A rs7086803 (SNP) in non-small cell lung cancer susceptibility and adiponectin receptorObjectiveFrom the above research results we can know AA genotype in VTI1A (rs7086803) SNP can easily lead to suffering from lung cancer. This part studies the correlation between susceptibility and adiponectin receptors.MethodsBased on the results of the first and second part, VTI1A (rs7086803) SNP AA genotype had easier lung cancer susceptibility than the type of AG and GG. Therefore, all patients were divided into three groups based on the VTI1A SNP genetic:1) AA group; 2) GG group; 3) AG group. With the random sample of 72 patients out of 887 patients with non-small cell lung cancer tissue and adjacent to carcinoma tissues, then analyzed the paraffin specimens by immunohistochemical method.Statistical analysis using SPSS 13.0 software with the result of the experiment; Groups of cases with immunohistochemical results of analysis using Kruskal-Wallis H test, the correlation between SNP genotypes and protein expression using Spearman’s Rank correlation analysis. Theoretical frequency is less than 5 analyzed by Fisher’s exact probability method. A two-sided P-value of<0.05 was defined as statistically significant.ResultsThere are 746 cases in non-small cell lung cancer group, randomly selected 71 patients into groups for analysis. The expression in tumor tissues with the AA genotype was significantly lower than that with other genotypes (mean rank:AA 18.55, AG 25.0, GG 45.76, P= 0.001). In adjacent non-tumor tissues, no statistically significant differences were observed between AdipoRl expression and VTI1A (rs7086803) polymorphism (mean rank:AA 37.45, AG 32.8, GG 37.98, P=0.544).In lung cancer tissues, the rank correlation coefficient between the SNP genotypes and the protein expression is 0.546, P< 0.001, the difference was statistically significant, there is a negative correlation relationship between two variables, the AdipoRl expression rate of carring AA loci is significantly lower than that of the other sites; In the tissue adjacent to carcinoma, the correlation analysis between SNP genotypes and protein expression was no statistically significant difference (P= 0.857).Conclusion1. The expression of AdipoRl protein in cancer tissue is lower than adjacent tissue of cancer.2. Adiponectin receptor 1 expression may be correlated with the expressioni of the allele A of VT11A.
Keywords/Search Tags:Non-small-cell lung cancer, Single nucleotide polymorphism, VTI1A, Smoking statues, Prognosis
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