| BackgroudColorectal caner (CRC), gastric cancer and liver cancer are the digestivesystem high-risk tumors. Statistically, in2008, incidences of CRC, gastriccancer and liver cancer were respectively third, fourth and fifth in men inthe world, preceded only by that of lung and prostate cancer; the incidenceof CRC was second only to that of breast cancer in women, and gastriccancer and liver cancer ranked respectively fifth and seventh. With thechange of dietary habits and life styles, overweight and obesity are widespread in the world, which attracts more attention of people. Recentresearches reveal that overweight and obesity increase cancer risk andprognosis, such as colorectal, gastric and liver cancer etc.Adiponectin is principally secreted by adipocytes. It is inverselyassociated with body fat, obesity, insulin resistance through stimulatinginsulin secretion, increasing fatty acid combustion and energy consumptionetc. It has been reported that circulating adiponectin level may inverselyassociated with the obesity-related cancer risk such as CRC, gastric cancer,breast cancer, and prostate cancer. It is reported that the action ofadiponectin is mediated by adiponectin receptors. There are two adiponectinreceptor forms (AdipoR1and AdipoR2) with unique distribution. AdipoR1is most abundant in skeletal muscle and also in endothelial cells and othertissues, whereas AdipoR2is predominantly expressed in the liver. Recently,the expression of AdipoR1and AdipoR2is reported in human CRC, gastric,lung, pancreatic, and prostate cancer.So far, there are numerous of epidemiological studies on the associationof circulating adionectin levels and risk or prognosis of CRC and gastriccancer and liver cancer, which were confirmed in the vivo and vitroexperiment. Several studies have reported polymorphisms of adiponectingene (ADIPOQ) are associated with circulating adiponectin levels andbiological function. It attracted our attention that single nucleotidepolymorphisms (SNPs) on ADIPOQ and AdipoR1gene (ADIPOR1) may contribute to the susceptibility of CRC and gastric cancer and liver cancer.Kaklamani et al. firstly evaluated the association of SNPs on ADIPOQ andADIPOR1with CRC risk. Several studies were also reported on theassociation of SNPs on ADIPOQ and ADIPOR1with CRC risk. However, theresults were consistent. In addition, researches on the association of SNPson ADIPOQ and ADIPOR1with prognosis of gastric cancer and risk of livercancer have not been reported yet.StudiesPart â… Objectives To further investigate the association of SNPs on ADIPOQand ADIPOR1with the CRC risk in Chinese population, and tosystematically evaluate association of SNPs on ADIPOQ and ADIPOR1withCRC risk via the meta-analysis methods.Methods The clinical case-control studies included341CRC patientsand726controls who were from thirty to eighty years old and recruited frompatients of three hospitals in Chong Qin. We exacted genomic DNA fromblood with Promega DNA Purification Wizard kit according to themanufacturer's instructions. We selected six most widely studied SNPs onADIPOQ (including rs2241766, rs266729, rs822395and rs1501299) andADIPOR1(including rs12733285and rs1342387). Genotyping of theselected SNPs were performed by the Taqman-MGB probes for SNPs allelicdiscrimination with a7900HT Fast Real-Time PCR System and SDSsoftware version2.3. The associations between genotypes of SNPs and riskof CRC were estimated by computing odds ratios (ORs) and their95%confidence intervals (CIs) with the common homozygote were recognized asthe reference using the unconditional logistic regression statistic model. Inaddition, in order to explore the association of the six potential associatedSNPs on ADIPOQ and ADIPOR1with CRC risk, we performed acomprehensive and systematic search of the PubMed, Medline and Embase databases updated to November of2011with the terms of "adiponectin","ADIPOQ","adipoenctin receptor1","ADIPOR1" and in combination with"colorectal cancer","colon cancer" or "rectal cancer" to identify studiesthat have evaluated the association of SNPs on the two genes and CRC risk.the pooled ORs and its95%CIs for the dominant genetic effect model of theselected SNPs were calculated using the fixed-effects model and the therandom-effects model.Results From our clinic case-control study on the association ofselected SNPs on the two with CRC risk, we found that rs266729onADIPOQ was not associated with the CRC risk with the adjusted OR was1.18(95%CI:0.91-1.54; CG+GG vs. CC). However, rs1342387on theADIPOR1was associated with a reduced risk for CRC with the adjusted ORwas0.74(95%CI:0.57-0.97; CT+TT vs.CC). Being consistent with ourclinic case-control study, meta-analysis studies also suggested that rs266729may not contribute to the CRC susceptibility (pooled OR=0.93,95%CI:0.81-1.08; CG+GG vs. CC) under the random-effects model. Meta-analysisalso found a significantly protective effects for rs1342387on CRC risk withthe pooled OR was0.79(95%CI:0.66-0.95; CT+TT vs. CC). No overallassociation with CRC risk was found for rs2241766, rs1501299, rs822395and rs12733285.Part â…¡Objective To evaluate the association of the selected SNPs on theADIPOQ and ADIPOR1genes with gastric cancer prognosis and risk inChinese population.Methods In the study of the association of the selected SNPs on the twogenes and gastic cancer prognosis, there were455patients of primarygastric cancer who have received gastrectomy treatment at the NantongTumor hospital from December2000to April2005. In the study of theassociation of the selected SNPs on the two genes and gastic cancer risk,there were137patients of primary gastric cancer as above and137normal controls from population who participated in the epidemiologic baselinesurvey of chronic and infectious disease in Nantong and surrounding regionsconducted by Nantong Tumor hospital from2003to2005. We extracted thegenomic DNA from formalin-fixed paraffin-embedded tissue specimenswith the QIAamp DNA FFPE Tissue Kit (Qiagene, Germany) according tothe manufacturer's instructions, and the genomic DNA from blood withsaturated NaCl method. The selection and genotyping methods of SNPs weresame as the part, however, rs2241766and rs1501299were excluded becauseof low call rate in the the genomic DNA extracted from formalin-fixedparaffin-embedded tissue specimens. The associations between genotypes ofSNPs and prognosis of gastric cancer were estimated by computing hazardratios (HRs) for gastric cancer mortality and95%CIs with the commonhomozygote were recognized as the reference using the partial likelihoodfor Cox's proportional hazards model. The associations between genotypesof SNPs and risk of gastric cancer were estimated by computing ORs andtheir95%CIs with the common homozygote were recognized as thereference using the unconditional logistic regression statistic model.Results From the clinical study on the association of selected SNPs onthe two genes with gastric cancer prognosis, we found no associationbetween rs266729and rs822395on ADIPOQ and gastric cancer motality. Sowere rs1342387and rs12733285on ADIPOR1. However, in the subjects ofwhom never drinking, rs266729was significantly associated with gastriccancer mortality (HR=0.74,95%CI:0.56-0.97, GG+CG vs. CC). Noassocitation between rs266729and gastric cancer mortality was detected inthe subjects of whom drinking. From the clinical case-control study on theassociation of ADIPOQ and ADIPOR1with gastric cancer risk, noassociation was detected between SNPs on the two genes and gastric cancerrisk.Part â…¢Objectives To evaluate the association of the selected SNPs on the ADIPOQ and ADIPOR1genes with liver cancer risk in Chinese population.Methods In the study of the association of the selected SNPs on the twogenes and liver cancer risk, there were109patients of primary liver cancerwho have received treatment at the Nantong Tumor hospital from2003to2005and109normal controls from population who participated in theepidemiologic baseline survey of chronic and infectious disease in Nantongand surrounding regions conducted by Nantong Tumor hospital from2003to2005. We extracted the genomic DNA from blood with saturated NaClmethod. The selection and genotyping methods of SNPs were same as thepart. The associations between genotypes of SNPs and risk of liver cancerwere estimated by computing ORs and their95%CIs with the commonhomozygote were recognized as the reference using the unconditionallogistic regression statistic model.Results From our clinic case-control study on the association ofselected SNPs on the two genes with liver cancer risk, we found significantassociation between vatiants rs2241766and liver cancer risk with OR was2.00(95%CI=1.16-3.45, p=0.013, TG+GG vs. TT) without being adjustedfor age, sex, smoking, drinking and HBsAg, but no association afteradjustment. There were no association of vatiants rs266729, rs822395andrs1501299on ADIPOQ with liver cancer risk. So were rs1342387andrs12733285on ADIPOR1.ConclusionThe studies suggested that rs1342387may be a novel factor for CRC riskand drinking might be an important factor influencing the association ofSNPs on ADIPOQ, rs266729expecially, with survival of gastric cancer. Inaddition, the negative results were found on the association of the selectedfour SNPs on the two genes with risk of gastric and liver cancer. |
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