Influence Of Interleukin 1 Beta Genetic Polymorphism, Smoking And Alcohol Drinking On The Risk Of Non-small Cell Lung Cancer

BackgroundPrimary bronchogenic carcinoma also called lung cancer, is one of the most common malignant tumors in China, the incidence and mortality rates are high and increasing year by year. The risk factor of lung cancer includes environmental and genetic factors, and their interactions. Among environmental factors, the status of smoking in the pathogenesis of lung cancer has been supported by various evidences. IL-1 gene was used as one common candidate gene for the study of interaction of environment and genes.IL-1 gene lies at the long arm of chromosome 2(2q13), including IL-1α,IL-1βand a specific receptor agonist IL-1ra. IL-1βis a key factor in the inflammatory response by the body, which has been proved to be an important mediator of inflammatory in the airway and was widely involved in airway inflammation.Zienolddiny S and other study found that IL-1β-31T/T and-511C/C increase the incidence of non-small cell lung cancer in Norwegian. Is there any association between polymorphisms of this two genes and the incidence of non-small cell lung cancer in Han people?At the same time, whether its effects are influenced by environmental and other factors? This article, basing on the analysis of pathology features and clinical presentation of lung cancer, studys the gene polymorphism of IL-1β-31,-511 and their interactions with environmental factors in occurrence of non-small cell lung cancer in Hans as well as its relevant mechanisms.ObjectiveTo analyze the relationship between pathological and clinical presentation of lung cancer, summarize the clinical characteristics of lung cancer and provide credible basis for the early diagnosis of lung cancer.To investigate the association of gene polymorphisms on chromosome 2 with the risks of non-small cell lung cancer. To find the interplay between the behavioral factors (such as drinking and smoking) with genetic polymorphisms in non-small cell lung cancer and its possible mechanisms.Methods329 lung cancer patients were diagnosed in ZhongNan hospital between 2002.1-2008.12.Their pathology type of cancer,age,gender, position of the cancer and clinical manifestations were analyzed one by one by the SPSS 13.0 software.A case-matched study was carried out to investigate the relations among gene, environment and the occurrence of lung cancer. Use the healthy questionnaire way to collect basic information of lung cancer patients and healthy collators about smoking and drinking, diet and so on. The healthy questionnaire mainly includes:Demography materials, smoking and drinking, diet custom, family history, formerly medical history and so on. Genetic polymorphisms of IL-1β-31T/T and-the 511C/C position were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP).The influence of IL-1βpromoter-31C/T's polymorphism on the IL-1βexpression was studied by gene cloning, carrier expression engineering.Linkage disequilibrium between the IL-1-31 and IL-1-511 was tested by estimation of haplotype frequencies performed by the SHEsis program. And OR of susceptibility of the genes to non-small cell lung cancer was analyzed by using multivariate logistic regression.ResultsThere are 329 (male 227, female 102) patients of lung cancer, aged 58.73±9.85 years old. Their pathologic diagnoses are as follows:adenocarci-noma 107 cases (32.5%), squamours cancer 145 cases (44.1%), adenosquamous carcinoma 49 cases (15.0%), small cell carcinoma 28 cases (8.5%). There are more male than female, especially in adenocarci-noma. The main pathological type is middle aged and elderly people. The central type was most common in squamours cancer and small cell carcinoma, while peripheral in adenocarci-noma. Most of them were of stageⅢorⅣof lung cancer.From the stepwise logistic regression analyses:smoking emerged as significant risk factor for non-small cell lung cancer (OR=10.13,95%CI:4.58-22.42) For IL-1-31 gene, the T/C genotypes represent the most common in the population. (OR=3.247,95%CI:1.794-5.878)For IL-1-511 gene, the T/C genotypes represent the most common in the population.The polymorphism of this gene is not related with non-small cell lung cancer.A linkage disequilibrium was revealed between IL-1-31 gene and IL-1-511 gene. (D =0.827, r2=0.785) Haplotype of IL-1β-31T/-511C significantly increased the incidence of non-small cell lung cancer. (OR=1.531,95%CI:1.163-2.814)A significant interaction showed between IL-1 gene and smoking, the incidence of non-small cell lung cancer on the risk of the genotype was related to smoking volume, among which IL-1β-31 T/T type-heavy smokers (15.246) have the highest risk.IL-1 gene also showed significant interaction with alcohol:mild alcohol consumption was not found to increase the risk of non-small cell lung cancer, but heavy drinking can increased the incidence of the individual,who carrier IL-1β-31 T/T type (OR=1.913) and IL-1β-511C/C type (OR=5.022).IL-1βpromoter-31T allele increased the expression of IL-1β.Conclusion1. In this study, smoking is still a risk factor of non-small cell lung cancer.2. Q13-q14 of the IL-1-31 and IL-1-511 genes, located on chromosome 2, had significant linkage disequilibrium. Polymorphism of IL-1-31T/C is highly related to non-small cell lung cancer.3. People who carriers IL-1-31T/T and IL-1-511C/C allele and smokes and have heavy alcohol consumption significantly increased the risk of non-small cell lung cancer.4. IL-1βpromoter-31T allele increases the expression of IL-1β.