Study On The Association Of SNPs Of Nm23Gene With The Risk Of Lung Cancer In North Chinese Human

Objective: Lung cancer is one of the most common malignant disease inour country and around the world, lung cancer is the first cause of cancerdeath worldwide. Nearly50years, the world, especially the industrializedcountries, lung cancer incidence and mortality are rising rapidly, died ofcancer of the male patients with lung cancer ranks first.1995,60thousandpeople died of lung cancer around the world and each year the number isrising, the mortality rate announced by the World Health Organization (WHO)in2003is1.1million/year, the incidence rate is1.2million/year. Because ofincidence of occult, rapid progress, lung cancer became a serious threat to thehealth of the people. Large amounts of data shows that its risk factors include:smoking, air pollution, occupational factors, chronic lung disease and thehuman internal factors such as genetic. But its pathogenesis has not yet beenelucidated. Some studies have found that the development of lung cancer andgenetic susceptibility are closely linked. therefore, to find susceptibility genes,high-risk group, early diagnosis is an effective way to improve lung cancersurvival rate.The nm23gene is a cDNA gene isolated from the mouse K-1735melanoma by steeg et al1988. Nm23is the first important gene for thesuppression of cancer metastasis, which is closely related to metastaticprogression in many types of human cancer including lung cancer. Thedecreased expression of its DNA or its gene product have a high correlationwith tumor metastasis. Single nucleotide polymorphism is the most commonpolymorphism in the genome, the general form is of a location in the genome,different individuals have different bases, but the groups in general are onlytwo possibilities bases. Moreover, the requirements of rare bases in the twopossible bases of frequency>1%, but the case of <1%claimed that this locus is mutated in some individuals rather than polymorphism. The SNP is the mostbasic elements of the genetic differences, with the development of molecularbiology and genetics and the study on loci single nucleotide polymorphism,people come to realize that single nucleotide polymorphisms is an importantrole in a variety of diseases. The rs16949649C/T and rs2302254C/T is atwo-nucleotide polymorphic loci in the nm23gene promoter region, a largenumber of studies have shown that they are associated with a variety of tumorrisk. But in different studies, the roles of nm23gene in the tumor developmentprocess are not the same, and the roles in the evolution of lung cancer are alsodifferent in different reports. Maybe nm23is not only a metastasis suppressorgene as its own under the concept. Its function has some tissue-specific andstage-specific. In different tumor diseases or different stages of tumorprogression, the role of nm23is different. In this paper, we studied theassociation between polymorphisms rs16949649C/T of nm23and the risk oflung cancer. By this way, we hope to offer some evidences for the preventionand therapy of lung cancer at molecular level.Methods: This study adopted case-cotrol research method. This studyincluded190lung cancer patients treated by surgery and190healthy controls.All the subjects were the Chinese Han people coming from Northern Chinaand there was no blood relationship among them. For DNAisolation,5mlvenous blood sample from each subject was collected. The DNAwas extracted from peripheral blood leukocytes by proteinase K digestion andsalting out procedure. The genotypes and alleles of the nm23rs16949649C/Twere analyzed by PCR-LDR. Statistical analysis was performed by usingSPSS13.0software package. The level of significance adopted was P<α=0.05was considered significant. Hardy-Weinberg analysis was performed bycomparing the observed and expected genotype frequencies in study groupsusing Chi-square test. The t test was used to examine the difference of agesbetween cases and controls. The Chi-square test was used to examine thedifference of sex between cases and controls. Univariate comparisons of alleleand genotype distribution were performed using Chi-square test. Non-conditional Logistic regression was performed to calculate the oddsratio(OR) and95%confidence interval(CI).Results:1The distribution of nm23rs16949649C/T genotypes among healthy controlswas compatible with those expected from Hardy-Weinberg equilibrium-(p>0.05).2The frequencies of C and T allele of nm23gene rs16949649C/T in cases andcontrols were:45.5%,54.5%and35.5%,64.5%There was statisticalsignificance of allele frequency between cases and controls(χ~2=7.883,P=0.005<0.05),and the OR of the C allele was1.517(95%CI=1.207-2.785).3The frequency distribution of the genotype TT,CT,CC in cases and controlswere:27.9%,53.2%,18.9%and40%,48.9%,11.1%. There was statisticalsignificance of genotype frequency distribution(χ~2=8.378,P=0.015<0.05).4Adjusted by smoke, OR and95%CI of the CC genotype against the CT+TTgenotype was1.888(1.053-3.384),p=0.033<0.05. There was statisticalsignificance.5Stratified by pathological type, the analysis showed no statisticalsignificance between the cases and controls in allele(P=0.963＞0.05)orgenotype (P=0.536＞0.05)distributions. But in the case of Squamous cellcarcinoma of lung, OR=2.551(95%CI=1.270-5.123) of the CC genotypeagainst the CT+TT genotype adjusted by smoke, P=0.008＜0.05. There wasstatistical significance.Conclusions: Among the Chinese Han people who come from NorthernChina, nm23gene rs16949649C/T polymorphism was associated with lungcancer, and the C allele was probably a susceptible gene of lung cancer. TheCC genotype was associated with the risk of lung squamous cell carcinoma.