Associations between hsa-miR-603 polymorphism, lifestyle-related factors and colorectal cancer risk.

BACKGROUND: Accumulated studies have suggested that single nucleotide polymorphisms (SNPs) in microRNAs are associated with risk of colorectal cancer (CRC). OBJECTIVE: We tested our hypothesis that rs11014002 in hsa-miR-603 may be associated with CRC risk with a crosstalk of life-related factors. METHODS: We conducted a case-control study which included 102 CRC patients and 204 matched cancer-free controls in Xiaoshan County. RESULTS: We observed that subjects with rs11014002 CT/TT genotype had an increased susceptibility for CRC (CT vs. CC: odds ratio (OR)=2.352, 95% confidence interval (CI): 1.142-4.840, P=0.020; CT+TT vs. CC: OR=2.031, 95% CI: 1.063-3.883, P=0.032). After stratification by lifestyle-related factors, similar results were found among nonsmokers (CT vs. CC: OR=2.753, 95% CI: 1.085-6.983, P=0.033; CT+TT vs. CC: OR=2.971, 95% CI: 1.188-7.435, P=0.020) and non-alcohol drinkers (CT+TT vs. CC: OR=3.279, 95% CI: 1.071-10.033, P=0.037). CONCLUSIONS: Our data suggest that hsa-miR-603 may be involved in colorectal tumorigenesis, and the genetic polymorphism in hsa-miR-603 is associated with CRC susceptibility.

A genetic variant in MiR-146a modifies digestive system cancer risk: a meta-analysis.

MicroRNAs (miRNAs) negatively regulate gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to digestive system cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed to identify all relevant studies published before August 31, 2013. A total of 21 independent case-control studies were included in this updated meta-analysis with 9,558 cases and 10,614 controls. We found that the miR-146a rs2910164 polymorphism was significantly associated with decreased risk of digestive system cancers in an allele model (OR=0.90, 95%CI 0.87-0.94), homozygote model (OR=0.84, 95%CI 0.77-0.91), dominant model (OR=0.90, 95%CI 0.84-0.96), and recessive model (OR=0.85, 95%CI 0.79-0.91), while in a heterozygous model (OR = 0.99, 95% CI 0.89-1.11) the association showed marginal significance. Subgroup analysis by cancer site revealed decreased risk in colorectal cancer above allele model (OR=0.90, 95%CI 0.83- 0.97) and homozygote model (OR=0.85, 95%CI 0.72-1.00). Similarly, decreased cancer risk was observed when compared with allele model (OR=0.87, 95%CI 0.81-0.93) and recessive model (OR=0.81, 95%CI 0.72-0.90) in gastric cancer. When stratified by ethnicity, genotyping methods and quality score, decreased cancer risks were also observed. This current meta-analysis indicated that miR-146a rs2910164 polymorphism may decrease the susceptibility to digestive system cancers, especially in Asian populations.

rs12904 polymorphism in the 3'UTR of EFNA1 is associated with colorectal cancer susceptibility in a Chinese population.

Accumulated evidence has indicated that Ephrin A1 (EFNA1) is associated with angiogenesis and tumorigenesis in various types of malignancies, including colorectal cancer (CRC). In the current study, we performed an online search using the public microarray database to investigate whether EFNA1 expression might be altered in CRC tissues. We then conducted a case-control study including 306 subjects (102 cases and 204 well-matched controls) in Xiaoshan County to assess any association between genetic polymorphisms in EFNA1 and CRC susceptibility. Searches in the Oncomine expression profiling database revealed EFNA1 to be overexpressed in CRC tissue compared with adjacent normal tissue. The rs12904 G-A variant located in the 3' untranslated region (UTR) of EFNA1 was observed to be associated with CRC susceptibility. Compared with the AA homozygous genotype, those carrying GA genotype had a decreased risk of developing CRC (odds ratio (OR) =0.469, 95% confidence interval (CI): 0.225-0.977, and P =0.043). The association was stronger among smokers and tea drinkers, however, no statistical evidence of interaction between rs12904 polymorphism and smoking or tea drinking on CRC risk was found. Our results suggest that EFNA1 is involved in colorectal tumorigenesis, and rs12904 A>G polymorphism in the 3' UTR of EFNA1 is associated with CRC susceptibility. Larger studies and further mechanistic investigations are warranted to confirm our findings.