| ObjectiveHuman8-oxoguanine glycosylase-1(hOGG1) is DNA repair gene. Itplays an important role on the base-excision repair. Many studies havealready reported the relationship between the SNP of hOGG1andpredisposition of bladder cancer, breast cancer, esophageal, cervical cancer.The present study at the molecular and gene level clarifies the relationbetween hOGG1and small cell lung cancer occurrence, development, toscreen susceptible population and improve the diagnosis of small cell lungcancer. It provides the theory basis and a new way of gene therapy for smallcell lung cancer pathogenesis.MethodsThe study has two parts. The first part: The expression of hOGG1wasdetected by immunohistochemistry in71cases of small cell lung cancerand30normal lung tissues. High and low expression group were definedaccording to the positive percentage of cells and staining intensity. Wecollected clinical data association with pathologic tissue. hOGG1and other factors was analyzed by the COX’s proportional hazard regression model topredict prognosis of small cell lung cancer. The second part:90cases smallcell lung cancer were investigated as well as90cases randomly selectedfrom the healthy check-up the same period as control group, matching twogroups according to age, sex and so on. Genomic DNA was extracted fromperipheral blood. The hOGG1Ser326Cys single nucleotide polymorphismswas tested and analyzed by the two primer-polymerase chain reaction(PCR-CTPP) technology; a control group variables, smoking and cancerpopulation differences between family history compared with cancer groupwas investigated by the chi-square test cases. Relationship of the SNP ofbases-repair hOGG1gene and the small cell lung cancer susceptibility andinteraction involving smoking and tumor familial history was analyzedwith the multiple logistic regression model. SPSS13.0software is used forthe statistics.ResultsProtein expression of hOGG1was noticed both in small cell lungcancer and normal lung tissues. The hOGG1expression of normal lungtissues mainly located in cytoplasm（60.0％）,while small cell lung cancertissues mainly located in caryoplasm（49.3％）, the expression of theirsub-cellular localization had a obvious difference（P<0.01）. The expressionof hOGG1in all normal lung tissues were low, while78.9percent of smallcell lung cancer tissues were high（P<0.01）. hOGG1expression was not related with gender, tumor staging, smoking index number, lymphaticmetastasis, nor hydrothorax（P>0.05）. There was a significant correlationbetween expression levels of hOGG1and prognosis by Kaplan-Meiersurvival Curve（P<0.05）, low expression of hOGG1patients’ mediansurvival time was23months, while high expression of hOGG1patients’median survival time was13months． COX multivariate proportionalhazards model analysis indicated hOGG1was a affecting survival as anindependent prognostic factor（P=0.004）. The proportion of hOGG1Ser326Cys genotype distribution: Ser/Ser(15.56%), Ser/Cys(44.44%),Cys/Cys(40.00%) in SCLC group, and Ser/Ser(8.89%), Ser/Cys(50.00%),Cys/Cys(41.11%) in control group. Logistic regression analysis showshOGG1Ser326Cys polymorphism and allele genetype distribution in SCLCand control group is not significantly correlation with the risk of small celllung cancer. Age, sex, smoking status and tumor familial history are subjectto statistical index, and the results indicate that the risk of individual withSer/Cys and Cys/Cys gene type, compare to Ser/Ser genotype, sufferingfrom small cell lung cancer increases, but does not reach statisticalsignificant level (P>0.05). Layered analysis shows hOGG1Ser326Cyspolymorphism and smoking have no significant synergistic effect to promoteSCLC (P>0.05).ConclusionHigh caryoplasm expression of hOGG1may associated with small cell lung cancer. High expression of hOGG1protein may indicate poorprognosis． hOGG1Ser326Cys polymorphism and allele genetypedistribution in SCLC and control group is not significantly correlation withthe risk of small cell lung cancer. Smoking and hOGG1ser326cyspolymorphism have no synergistic effect for small cell lung cancerpredisposition. |
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