Dataset Information

A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk.

ABSTRACT: Genome-wide association studies (GWAS) on colorectal cancer (CRC) have identified dozens of single nucleotide polymorphisms (SNPs) in more than 19 independent loci associated with CRC. Due to the heterogeneity of the studied subjects and the contrary results, it is challenging to verify the certainty of the association between these loci and CRC.We conducted a critical review of the published studies of SNPs associated with CRC. Five most frequently reported SNPs, which are rs6983267/8q24.21, rs4939827/18q21.1, rs10795668/10p14, rs4444235/14q22.2 and rs4779584/ 15q13.3, were selected for the current study from the qualified studies. Then meta-analyses based on larger sample sizes with average of 33,000 CRC cases and 34,000 controls were performed to assess the association between SNPs and CRC risk. Heterogeneity among studies and publication bias were assessed by the ?2-based Q statistic test Begg's funnel plot or Egger's test, respectively.Our meta-analysis confirmed significant associations of the five SNPs with CRC risk under different genetic models. Two risk variants at rs6983267 {Odds Ratio (OR) 1.388, 95% Confidence Interval (CI) 1.180-1.8633} and rs10795668 (OR 1.323, 95% CI 1.062-1.648) had the highest ORs in homogeneous model. While ORs of the other three variants at rs4939827 {OR 1.298, 95% CI 1.135-1.483}, rs4779584 (OR 1.261, 95% CI 1.146-1.386) and rs4444235 (OR 1.160, 95% CI 1.106-1.216) were also statistically significant. Sensitivity analyses and publication bias assessment indicated the robust stability and reliability of the results.

SUBMITTER: Hong Y

PROVIDER: S-EPMC5342026 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk.

Hong Yi Y Wu Guoying G Li Wei W Liu Dahai D He Kan K

Oncotarget 20161101 45

Genome-wide association studies (GWAS) on colorectal cancer (CRC) have identified dozens of single nucleotide polymorphisms (SNPs) in more than 19 independent loci associated with CRC. Due to the heterogeneity of the studied subjects and the contrary results, it is challenging to verify the certainty of the association between these loci and CRC.We conducted a critical review of the published studies of SNPs associated with CRC. Five most frequently reported SNPs, which are rs6983267/8q24.21, rs ...[more]

PMID: 27661122

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Project description:BackgroundIncreasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk.MethodsWe systematically searched Embase and Medline databases to identify eligible studies that examined the associations of different types of Fas with CRC risk. The effect estimates and their 95% confidence intervals (Cis) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to examine the robustness of the study findings.ResultsThis study evaluated the associations of 28 dietary and 18 blood Fas with CRC risk by summarizing the most updated evidence from 54 observational and four Mendelian Randomization (MR) studies. The present findings suggested that high dietary intake of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and docosapentaenoic acid (DPA) are related to low risk of CRC, while the n-6/n-3 PUFA ratio and trans-FA are related to high risk of CRC. The summary of all cohort studies found that a high intake of SFA and DHA was a protective factor for CRC, and a high intake of the n-6/n-3 PUFA ratio was a risk factor for CRC. In the subgroup analysis of cancer subsites, we found that the dietary intake of linoleic acid (LA) and trans-FA are risk factors, while DPA is a protective factor for colon cancer. High dietary DHA intake was associated with a lower risk of rectal cancer, while the dietary n-6/n-3 PUFA ratio was associated with a higher risk of rectal cancer. Meta-analysis of blood FA levels showed a significant reverse association between blood pentadecanoic acid and CRC risk, whilst other blood Fas showed no significant association with CRC risk. All included MR studies showed that high plasma arachidonic acid (AA) is associated with increased CRC risk.ConclusionsCurrent evidence on the dietary intake and blood levels of Fas in relation to CRC risk is less consistent. Future studies are needed to investigate how the metabolism of Fas contributes to CRC development.

Project description:BackgroundVascular endothelial growth factor (VEGF) is a key mediator that plays an important role in angiogenesis, tumor growth, and tumor metastasis. The associations between five polymorphisms of VEGF (rs3025039, rs699947, rs10434, rs1570360, and rs2010963) and renal cell carcinoma (RCC) risk have been extensively investigated, but the currently available results are inconsistent and inconclusive. To obtain a more accurate assessment of the associations, we conducted a meta-analysis in this study.Materials and methodsRelevant studies were collected systemically from the following three electronic databases: MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). Statistical analyses were performed using Review Manager 5.2 in a fixed- or random-effects model. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to establish the strength of associations.ResultsA total of eight case-control studies with 1,936 RCC cases and 2,770 controls fulfilling the inclusion criteria were selected for this meta-analysis. The pooled OR indicated that rs699947 polymorphism was significantly associated with RCC risk in all genetic models. A significant association was also found between the rs3025039 polymorphism and RCC risk in a homozygous model (TT vs CC: OR =1.38, 95% CI =1.11-1.72, P=0.004), a dominant model (CT+TT vs CC: OR =1.21, 95% CI =1.05-1.39, P=0.01), and a recessive model (TT vs CC+CT: OR =1.28, 95% CI =1.04-1.57, P=0.02). After a subgroup analysis of ethnicity in the allele contrast model of rs3025039 polymorphism, we found a significant relationship in the allele contrast model (T vs C: OR =1.21, 95% CI =1.05-1.40, P=0.007) in the Asian population. With regard to rs10434 polymorphism, significant association was observed only in a homozygous model (GG vs AA: OR =0.75, 95% CI =0.57-0.98, P=0.03). As to rs1570360 or rs2010963, we did not observe any relationship between the two polymorphisms and RCC risk in our study.ConclusionOur meta-analysis confirmed the fact that rs699947, rs3025039, and rs10434 polymorphisms were significantly relevant to elevated RCC risk. In the meanwhile, this study also demonstrated that the allele contrast model of rs3025039 polymorphism was likely to be associated with risk of RCC in the Asian population.

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Dataset Information

A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk.

Publications

A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk.

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