| Objective: Lung cancer is one of the most common malignant tumor.Itis a serious threat to human health and life, in recent years, as environmentalpollution and life rhythm speeding up, the incidence and mortality rates areincreasing year by year, the growth of the incidence and mortality rate are alsoin the first place in tumors. In the world, there are about more than110millonpersons died of lung cancer in a year, about17.8%of the total cancer deaths,although the5years survival rate of stage I in lung cancer can be reachedabout70%, the overall5-year survival rate less than15%, the reason is thatabout8patients in ten has belongd to advanced lung cancer, and these patientshad lost the chance of operation. So earlier diagnosis can improve the survivalof lung cancer. The pathogenesis of lung cancer is not very clear at present. Inclinical, early diagnosis and treatment for lung cancer also have no idealmethod.smoking is one of risk factor determinly, but some of long-termsmoking persons not suffering from lung cancer and some never smokingpersons suffering from lung cancer. It shows that in addition to someenvironmental factors, suffering from lung cancer also having association withgene.In addition to the mature of red blood cells, other cells all havemitochondria in human, mitochondria is an important organelles ineukaryotes, and is the center of energy metabolism, In metabolism,apoptosis,aging process of physiologyand pathology, mitochondria also plays animportant role in eukaryotic cells. Mitochondrial DNA (mtDNA) is the onlyone discoveried genetic material outside cell nucleus and it can complete theprocess of copying transcription and translation independed. All of theMtDNA gene sequences were completed by Aderson in1981for the first time, Those sequences were also known as Combridge sequences. Those were oftenused as reference sequence in the study of mitochondrial DNA in human.Human mitochondrial genome is a16kb length, closed-circular, duplexmolecule that containing37genes, two ribosome RNAs, and a complete setsof22tRNA. Because of lackling of protective histones, limited capacity forDNA repair, exposure to high levels of reactive oxygen species(ROS)generated in mitochondria, and at the same time, mitochondria DNA is in thehigher oxygen environment directly, easying to produce oxygen free radicals,mitochondrial DNA is believed to be more susceptible to DNA damage andacuquired mutations at a higher rate than nuclear DNA(nDNA). Thus somaticmtDNA mutation occur in a wide variety of degenerative,metabolic diseasesand cancer.Mitochondrial DNA can be divided into coding region andnoncoding region,displacement loop is the noncoding region,and locatedbetween the tRNAPhe and tRNApro, the length about1122bp(16024-576),Because that this region contains more A and T bases, and It is the palce thatmitochondrial membrane and mitochondrial DNA combining, and easying tobe damaged by lipid peroxide. It is also important for both replication andexpression of the mitochondrial genome.Most somatic mutations andpolymorphisms accurate in a hotspot in mtDNA noncoding region.In recent years, polymorphisms in displacement loop are foung in manyother cancer patients, such as the liver cell cancer, gastrointestinal tumors,headand neck cancer,breast cancer. And different cancers have polymorphismsdifferently.But polymorphisms in displacement loop were rarely studied inlung cancer.In this study, we try to find the association between lung cancerand polymorphism in D-loop though sequencing blood mitochondrial D-loopof lung cancer pationts and normal persons. Contrasting the differences in lungcancer and normal persons to find out that there were associations in the singlenucleotide polymorphisms of D-loop and having lung cancer, and analyzeaction in the the geneenvironment(smoking), and provides geneticsusceptibility mark to helping to diagnose lung cancer.Methods:121cases of lung cancer,from2001to2011treated in the fourth hospital of HeBei Medical University, diagnosed by histopathology, and91cases of the normal physical examination, we used Polymerase chainreaction and sequenced blood mitochondrial D-loop of lung cancer patientsand normal controls to identify these differences, Statistical analysis wasperformed using chi-square test and Fisher's extact test in SPSS13.0softwarepackage, the statistical results is significance if the P <0.05.Results:1Comparing the clinical data between lung cancer group and control group,There were no statistical difference of Age,sex(P=0.969,0.114)in the twogroups, while smoking was statistical different between the two groups (P=0.003).2Compared the sequences of mtDNA with the Cambridge sequence, wefound174polymorphic loci in the121cases with lung cancer, and themulti-state rate was17.72%; also found that174polymorphic loci in thecontrol group. There was no significant between the two groups(χ2=19.260,P=0.000).3We counted the number of variations according to gender, age, pathologydifferently in the case group, we found that737variations in73male and472variations in48female patients;959variations in96patients who was>50years old,250variations in25patients who was≤50years old,291variationsin28patients who was squamous cell carcinoma patients, and629variations in65patients who was adenocarcinoma patients while289variations in28patients who was small cell lung cancer patients. The results indicated thatthere were no significance at variations number of nucleotides in aging, sex,and pathological types differently.4In this study, the frequency of A deletion at16247sites in the lung cancergroup is higher than in the control group(5.8%vs.0%, P=0.018); thefrequency of T/C at489sites in the lung cancer group is higher than in thecontrol group(58.7%vs.46.2%, P=0.047, OR=1.657,95%CI=0.957~2.867).5We had analysised the risk of having lung cancer in above two Single nucleotide polymorphisms according to smoking or not. In the groups whowere smoking, the frequency of A deletion at16247site in the lung cancergroup is higher than in the control group (7.1%vs.0%, P=0.018); thefrequency of T/C at489site in the lung cancer group is higher than in thecontrol group(50.0%vs.41.7%,),it was no statistically significant in abovegroup(P＞0.05).In no-smoking groups, at16247site, it was4.6%having A deletion in thelung cancer group and0%having A deletion in the control group, it was nostatistically significant(P＞0.05);at489site,it was66.2%having T/Cmutation in the lung cancer group,but only47.8%in the control group, it wasstatistically significan(tP=0.037,OR=2.138,95%CI=1.059~4.316). a personwho carrying C had2.138times)risk of having lung cancer than that carryingT except for the effects of smoking.At489site, a person who smoking and carrying C had4.455times risk thanthat who non-Smoking and carrying T, a person who smoking and carrying Thad3.182times risk than that who non-Smoking and carrying the same base,and a person who non-smoking and carrying C had2.138times risk than thatwho non-Smoking and carrying T.Conclusion:1In this study, smoking is still a environmental risk factor of lung cancer.2A deletion at16247site and having C base at489site can increase the riskof having lung cancer, the risk of a person who carrying C is1.657times thanthat carrying T.3The variations number of nucleotides in D-loop of lung cancer have noassocication to aging, sex, and pathological types.4It is having interaction between smoking and single nucleotidepolymorphism At nucleotide489, the bases at this nucleotide and the numberof cigarettes variations can increase the risk of having lung cancer. the highestrisk is the persons who having C bases and also smoking. |
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