| Backgrounds and ObjectivesColorectal cancer (CRC) is the most common digestive malignant tumor in developed countries and its morbidity and mortality rates kept rising in the past decades worldwide. With the development of economy and society, environmental factors including dietary, lifestyle-related factors kept changing and the incidence rate of CRC in developing countries kept rising year after year in the same time.Tumorigenesis of CRC is a multi-step process and could be affected by various factors including dietary intake, lifestyle-related factors and genetic factors. As a class of non-coding RNAs, miRNA was found to play key roles on regulation of gene expression and implicated in colorectal carcinogenesis. The single nucleotide polymorphisms (SNPs) in miRNA coding regions and miRNA binding sites were found to be involved in miRNA expression and modified biological functions.In the present study, a series of SNPs in miRNA coding regions and binding sites were selected and their associations with CRC risk, as well as their interactions with lifestyle-related factors in Chinese population remain unclear. Information of lifestyle factors and dietary intake was collected in the population-based control study. Objective of the study was to explore the associations of lifestyle-related factors and genetic variants with CRC risk and explore their interactions on colorectal carcinogenesis. Materials and MethodsThe research was carried out with a population-based case-control study in Jiashan county, Zhejiang province.478cases diagnosed with CRC during from2002to2008were recruited in the present study and the controls matched with cases by age, sex and resident areas were enrolled in the same periods, and477healthy controls were included eventually. A structured questionnaire was used and social-demographic characteristics including age, sex, occupation, educational level and information of dietary intake and lifestyle-related factors were collected by face to face interview. After interview,3-5venous blood of each participant was acquired and genomic DNA was isolated. Genetic variants in miR-605(rs2043556), miR-149(rs2292832), miR-423(rs6505162), miR-608(rs4919510), miR-27a(rs895819), miR-196a-2(rs11614913), miR-618(rs2682818), miR-943(rs1077020) encoding regions and miRNA binding sites in3'UTRs of FBXO39(rs4239266), TP53BP2(rs17739), Rab24(rs1128287), DNFF-beta(rs10909818), GALN(rs1141390),,ABCAl(rs4149338),ABDAl(rs4149339) and ADARB2(rs904960), PKNOX1(rs2839629) were selected and their biological functions were evaluateded with bioinformatics software. Genotypes of the SNPs were detected with polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP). Software of SPSS version13.0was employed in the present study and associations of the SNPs and lifestyle-related factors with CRC risk were analyzed, and odds ratios (ORs) as well as95%confidence intervals (95%CIs) were computed. Interactions between the genetic variants and lifestyle-related factors were assessd with stratified analysis. A p-value less than0.05is regarded to be significant.ResultsBody mass index (BMI) at diagnosis less than19was related to increased colorectal cancer risk (OR=1.51,95%CI:1.05-2.18) and the characteristic preferred to be associated with female CRC (OR=1.75,95%CI:1.05-2.93) risk, but not with male CRC risk after stratification by sex. No significant association was observed between alcohol consumption and CRC risk, however high-alcoholicity liquor intake might be able to increase CRC risk (OR=1.69,95%CI:0.94-3.05) and consumption amount per week was associated with increased CRC risk (OR=1.02,95%CI:1.01-1.04). Drinking green tea or drinking tea for more than20years could reduce CRC risk, and the ORs were0.64(95%CI:0.45-0.91) and0.68(95%CI:0.47-0.99), respectively. Salt meat intake might be a potential risk factor of CRC (OR=1.28,95%CI:0.99-1.69) and irritability could increase male CRC risk (OR=1.51,95%CI:1.02-2.22), but not increase female CRC risk.In the present study, we found that SNPs within miR-423(AC/AA vs. CC) and miR-605(AG/GG vs. AA) encoding regions were associated with reduced rectal cancer risk and the ORs were0.65(95%CI:0.43-0.98) and0.66(95%CI:0.45-0.96), respectively, while the SNP in pre-miR-149(CT/CC vs. TT) was associated increased colon cancer risk (OR=1.58,95%CI:1.05-2.36). SNP in pre-miR-27a (CT/CC vs. TT) was associated with increased female CRC risk (OR=1.52,95%CI:1.02-2.06) and that in pre-miR-618might be associated CRC risk of those had salt meat for less than1time per month and the OR was1.46(95%CI:0.99-2.17).The SNP (rsl128287) in3'UTR of Rab2'4was associated with increased CRC risk (AA vs. AC/CC, OR=1.74,95%CI:1.27-2.37) and after stratification by lifestyle-related factors, significant associations between the SNP (AA vs. CC) and CRC risk was observed among the non-smokers (OR=1.90,95%CI:1.21-3.00), those had salt meat for less than1time per month (OR=2.00,95%CI:1.18-3.40) and didn't drink tea (OR=2.00,95%CI:1.21-3.30). In addition, a significant association was detected among those engaged in alcohol consumption in recessive model (AA vs. AC/CC, OR=2.13,95%CI:1.11-4.08).For the SNP (rs17739) in3'UTR TP53BP2, no significant association was observed among all the subjects, however significant associations were detected between the SNP (CT/TT vs. CC) and CRC risk among those drank tea (OR=0.66,95%CI:0.44-0.98), those with alcohol consumption (OR=0.57,95%CI:0.34-0.96) and had salt meat more than and equal to1time per month (OR=0.65,95%CI:0.44-0.96). Among those drank tea, a significant association was observed between the SNP (rs10909818) in3'UTR of DNFF-β (AG/AA vs. GG, OR=1.83,95%CI:1.22-2.75) and a similar association was observed among the smokers (OR=1.60,95%CI:1.02-2.51).Conclusions(1) BMI less than19might be a indicator of CRC incidence and high-alcoholicity liquor consumption amount was able to increase CRC risk, while drinking green tea or drinking tea for more than20years could reduce CRC risk.(2) Genetic variants in pre-miR-423and pre-miR-605was associated with reduced rectal cancer risk, while that located within pre-miR-149was associated with increased conlon cancer risk. The SNP in pre-miR-27a was associated with increased female CRC risk.(3)The SNP (rsl128287) in3'UTR of Rab24was associated increased CRC risk and the SNP might be able to interact with smoking, salt meat intake, tea consumption and alcohol drink. The SNP (rs17739) in3'UTR of TP53BP2had potential of interacting with tea and alcohol drinking and salt meat intake to modify CRC risk. SNP (rs10909818) in3'UTR of DNFF-β could interact with tea drinking and smoking to modify CRC risk.
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