Relationship Of RYBP Gene Polymorphisms With NSCLC

ObjectiveLung cancer as one of the most commonly diagnosed cancers as well as the leading cause of cancer death globally. Now non-small cell lung cancer(NSCLC) accounts for about 80% of all lung cancer, the overall 5-year survival rate of patients with lung cancer is about 16%. More and more studies have demonstrated that genetic variations play the important role in lung cancer development and prognosis besides environmental factors. The main treatments on non-small lung cancer are radical surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, radiotherapy and targeted therapy. Although these years the medical profession has made some progress in the early diagnosis, radical surgery, chemotherapy, radiation and chemotherapy and targeted therapy of non-small cell lung cancer, the incidence rate and mortality of non-small cell lung cancer ramained increasing in last decades. Thus studying genes related to NSCLC, and finding new target genes for diagnosis and treatments of NSCLC, are important with experimental and clinical significances. RYBP has been identified as the member of Pc G family recently. In addition to its gene transcriptional regulation due to the component of PRC1 complex, RYBP is involves in apoptosis, cell cycle control and cell invasion. Up to now, there are rare studies on RYBP in carcinogesis and development and the results are inconsistent. Moreover, it is still not clear about the clinical significance of RYBP as a novel tumor suppressor. In this present study, we combined Tag SNP and potential functional SNP to survey all of the SNP of RYBP gene, and conducted a case-control study and a prospective cohort study respectively to explore the associations between the SNP of RYBP gene and non-small cell lung cancer susceptibility and survival in Chinese population in order to provide scientific basis for the tertiary prevention of lung cancer, and provides clues for reasonable clinical decision and individualized treatment. We analyze that the relationship between RYBP m RNA, protein expression and the SNP, and verify the relationship by TCGA database.Method1. A hospital-based case-control study was conducted in Tianjin Medical University Cancer Hospital and Institute, consisted of 603 histopathologically confirmed incident NSCLC patients and 661 cancer-free controls. All the controls were randomly selected from a community-based screening program and were frequency-matched to the patients on sex and age.2. SNP of RYBP gene was assessed by Taq Man method. By comparing the case group and the control group the difference of genotype frequency distribution, calculated the relative risk of lung cancer, and analysis the relationship of RYBP gene SNP with NSCLC. Respectively using tissue microarray and real-time quantitative PCR technology measures protein expression and m RNA expression.3. The program SPSS sortware package(version 19.0, SPSS Inc., Chicago, IL, USA) and Graphpad Prism 5.0(Graphpad Software Inc., La Jolla, CA) were utilized for all statistical analyses. Chi-square test was used to analysis the general demographic characteristics of patients and the control group, the main environmental factors, genotypes of the research object. NSCLC risk factors analysis were applied to single factor and multi factor non-conditional logistic regression analysis estimated risk(Odds Ratio, OR) and adjusted or value(Adjusted Odds Ratio, ORa) and 95% confidence intervals(95% Confidence Intervals, 95% CI). Kaplan-Meier method and log-rank test were used for survival analysis. Cox's Proportional Hazard Model was used to estimate the relationship(Hazard Ratio, HR) between RYBP gene SNP and patients' survival in univariate and multivariate analyses. All tests were two-sided tes, test level ? = 0.05, P <0.05 was considered statistically significant.Results1. RYBP rs4676875,RYBP rs12631820,RYBP rs2118593,RYBP rs4677152 were associated with decreased non-small cell lung cancer susceptibility.2. Stratified analysis found rs4676875 was associated with male, age?60, age>60, no-smoking history and no-family history of cancer with NSCLC; rs12631820 was associated with male,age?60, age>60, no-smoking history and no-family history of cancer with NSCLC; rs2118593 was associated with male, female,age?60, age>60, smoking history, no-smoking history, family history of cancer and no-family history of cancer with NSCLC; rs17009699 was associated with male, age?60 and no-family history of cancer with NSCLC. Gene site-site interaction revealed that individuals with three putative high-conservation genotypes statistically decreased NSCLC risk(OR:0.09,95%CI:0.03-0.27).3. RYBP rs4676875?RYBP rs12631820?RYBP rs2118593?RYBP rs4677152 ?RYBP rs12956? RYBP rs17009699 were not associated with the prognosis of NSCLC.4. Stratified analysis found rs4676875 was associated with the prognosis of BMI>24 NSCLC; rs12631820 was associated with BMI>24 NSCLC prognosis; rs2118593 was associated with the prognosis of early-stage(?+?) of NSCLC; rs4677152 was associated with female and adenocarcinoma NSCLC prognosis.5. RYBP rs2118593 genotype in the female group was associated with RYBP m RNA expression(P < 0.05). RYBP rs2118593 genotype was associated with RYBP TMA score(P < 0.05).6. RYBP average expression level in the NSCLC tissue was lower than tissue adjacent to carcinoma.Conclusions1. RYBP related gene SNP was associated with NSCLC risk.2. RYBP related gene SNP was associated with prognosis of NSCLC.3. RYBP related gene SNP was associated with RYBP mRNA and its protein expression.