Colorectal Cancer In Caucasians Research Articles

E-cadherin (CDH1) gene -160C/A polymorphism and the risk of colorectal cancer: A meta-analysis involving 17,291 subjects.

The E-cadherin (CDH1) polymorphism has been implicated in the susceptibility to colorectal cancer (CRC). However, the results remain inconclusive. The present meta-analysis aimed to investigate the association between the CDH1-160C/A polymorphism and CRC risk. Relevant studies were retrieved by searching PubMed, Web of Science, Google Scholar, the Cochrane Library, Embase, CNKI and Wanfang databases up to 11 March 2021. Pooled odds ratio and 95% confidence interval were calculated using either the fixed- or random-effects model. Quality evaluation was carried out using Newcastle-Ottawa Scale (NOS). A trial sequential analysis (TSA) was conducted to reduce the risk of type I error. In total, 16 studies from 14 articles with 8699 patients and 8592 controls were included. In general, all studies were of high quality (NOS score higher than 6). Overall, no significant associations between the CDH1 -160C/A polymorphism and CRC risk were detected. In subgroup analysis by ethnicity, source of control, genotyping method and location, significant associations were found between the CDH1-160C/A polymorphism and the risk of CRC in the Caucasians and the hospital-based subgroup. Furthermore, 10 studies with 8019 subjects reported the association between the polymorphism and clinical characteristics in CRC patients, and we found that the CDH1-160C/A polymorphism might show a protective role in the distal CRC subgroup. By TSA, the findings in the present study were based on sufficient evidence in Caucasians, but not in Asians. This meta-analysis suggests that the CDH1-160C/A polymorphism may be an important protective factor for CRC in Caucasians and a hospital-based subgroup. Moreover, the polymorphism show a protective role in the distal CRC group. However, large and well-designed studies are warranted to validate our findings, especially for Asians.

COX-2 gene rs689466 polymorphism is associated with increased risk of colorectal cancer among Caucasians: a meta-analysis

BackgroundSeveral studies have reported the Cyclooxygenase 2 (COX-2) rs689466 polymorphism as a susceptibility locus of colorectal cancer (CRC), but their findings are inconsistent. Thus, this meta-analysis was performed to more accurately identify the effects of this polymorphism on CRC risk.MethodsPotential case-control studies on EMBASE, Google Scholar, Web of Science, Cochrane Library, and PubMed were searched. The strength of association was quantified by pooled odds ratio and 95% confidence interval. Totally 16 articles involving 8998 cases and 11,917 controls were included.ResultsNone of the five tested genetic models revealed an association between rs689466 polymorphism and CRC risk. Stratified analysis by ethnicity uncovered a positive association between this polymorphism and higher CRC risk in Caucasians, but not in Asians. In addition, we found that high expression of COX-2 was associated with better overall survival for all CRC patients.ConclusionTo sum up, the COX-2 rs689466 polymorphism may be related with susceptibility to CRC in Caucasians. This finding should be verified by larger-size studies with different ethnic groups.

Associations of tumor necrosis factor-α polymorphisms with the risk of colorectal cancer: a meta-analysis

Background: Recently, the roles of tumor necrosis factor-α (TNF-α) polymorphisms in colorectal cancer (CRC) were analyzed by some pilot studies, with inconsistent results. Therefore, we performed the present study to better assess the relationship between TNF-α polymorphisms and the risk of CRC.Methods: Eligible studies were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess correlations between TNF-α polymorphisms and CRC.Results: A total of 22 studies were included for analyses. A significant association with the risk of CRC was detected for TNF-α -308 G/A (recessive model: P = 0.004, OR = 1.42, 95%CI 1.12–1.79) polymorphism in overall analyses. Further subgroup analyses based on ethnicity of participants revealed that TNF-α -238 G/A was significantly correlated with the risk of CRC in Caucasians (dominant model: P = 0.01, OR = 0.47, 95%CI 0.26–0.86; overdominant model: P = 0.01, OR = 2.27, 95%CI 1.20–4.30; allele model: P = 0.02, OR = 0.51, 95%CI 0.29–0.90), while -308 G/A polymorphism was significantly correlated with the risk of CRC in Asians (recessive model: P = 0.001, OR = 2.23, 95%CI 1.38–3.63).Conclusions: Our findings indicated that TNF-α -238 G/A polymorphism may serve as a potential biological marker for CRC in Caucasians, and TNF-α -308 G/A polymorphism may serve as a potential biological marker for CRC in Asians.

Prognostic and clinicopathological value of p16 protein aberrant expression in colorectal cancer: A PRISMA-compliant Meta-analysis.

Purpose:Several studies have examined the potential role of p16 protein expression as a diagnostic and prognostic biomarker in various cancers. However, it remains unclear whether p16 protein expression is a prognostic and diagnostic factor for colorectal cancer. Therefore, this meta-analysis is conducted to evaluate the associations of p16 protein expression with overall survival (OS) and clinicopathological characteristics of colorectal cancer.Methods:According to PRISMA guideline, relevant literatures were identified by searching Medicine, Web of Science, WanFang, and CNKI databases. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from included studies to assess the association between p16 protein expression and OS of patients with colorectal cancer. Other relevant data were extracted to evaluate the correlations of p16 protein expression with risk and clinicopathological characteristics of colorectal cancer. Stata 12.0 software was applied to calculate the strength of association between p16 protein expression and colorectal cancer.Results:Forty-one studies were included to evaluate the association between p16 protein expression and colorectal cancer. Nine studies involving 1731 patients with colorectal cancer found that there was no association between p16 protein expression and OS of colorectal cancer in the overall analysis (HR = 0.78, 95% CI: 0.55–1.10). However, p16 protein overexpression was significantly associated with a better prognosis in patients with colorectal cancer when cut-off value of p16 protein expression was <10% (HR = 0.23, 95% CI: 0.08–0.66). The results of subgroup analysis based on ethnicity indicated that p16 protein overexpression was a risk factor for the occurrence of colorectal cancer in Caucasians (odds ratio = 28.95, 95% CI: 6.08–137.89), but not in Asians. Furthermore, p16 protein overexpression was significantly associated with the Dukes stage, lymph node metastasis, tumor location, and Tumor Lymph Node Metastasis-stage of colorectal cancer.Conclusions:p16 protein overexpression might be a useful biomarker to predict the clinicopathological progress and prognosis of colorectal cancer.

Association between 8q24 rs6983267 polymorphism and cancer susceptibility: a meta-analysis involving 170,737 subjects.

Published data on the association between 8q24 rs6983267 polymorphism and cancer risk are inconsistent. Thus, we conducted a meta-analysis to evaluate the relationship between rs6983267 polymorphism and cancer risk. We searched on PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) up to November 1, 2016 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of this association. We included 78 case-control studies with a total of 73,996 cases and 96,741 controls in this meta-analysis. The pooled results showed that rs6983267 polymorphism was significantly associated with increased risk of overall cancer in all genetic models (dominant model: OR = 1.19, 95% CI = 1.13–1.26; recessive model: OR = 1.19, 95% CI = 1.14–1.25; homozygous model: OR= 1.31, 95% CI = 1.23–1.40; heterozygous model: OR = 1.14, 95% CI = 1.10–1.19; allelic model: OR = 1.14, 95% CI = 1.11–1.18). Stratified analyses indicated that rs6983267 significantly increased the risk of colorectal cancer in Caucasians, prostate cancer in Caucasians and Asians, thyroid cancer in Caucasians and lung cancer in Asians. When studies were stratified by study quality, source of controls and genotyping method, significant associations were especially found in the high quality studies, the publication-based studies, the hospital-based studies, and the PCR-RFLP studies. Additional well-designed studies with large samples should be performed to validate our results.

Association between the Epithelial Cadherin - 160C/A Polymorphism and Colorectal Cancer Risk: Evidence from a Meta-Analysis.

The aim of the present study was to assess the association between the epithelial cadherin (CDH1) -160C/A polymorphism and colorectal cancer (CRC) using a meta-analysis. A literature search of PubMed, Embase, and Web of Science databases was performed for relevant studies. Statistical analyses were carried out using Stata 12.0 to combine all of the relevant studies. Odds ratio (OR) with 95% confidence interval (CI) values were applied to evaluate the strength of the association. Eight studies with 7231 cases and 7080 controls were included. The meta-analysis results showed that the CDH1 -160C/A polymorphism was significantly associated with CRC risk (AA vs. CC: OR = 0.98, 95% CI = 0.71-1.36; CA vs. CC: OR = 0.92, 95% CI = 0.86-0.99; dominant model: OR = 1.01, 95% CI = 0.81-1.26; recessive model: OR = 0.91, 95% CI = 0.81-1.02). In the subgroup analysis based on ethnicity, significant association was found between the CDH1 -160C > A polymorphism and CRC risk in Caucasians. In conclusion, the CDH1 -160C/A polymorphism may be a susceptible predictor for the risk of CRC in Caucasians.

Quantitative Assessment of the Association between Genetic Variants in MicroRNAs and Colorectal Cancer Risk.

Background. The associations between polymorphisms in microRNAs and the susceptibility of colorectal cancer (CRC) were inconsistent in previous studies. This study aims to quantify the strength of the correlation between the four common polymorphisms among microRNAs (hsa-mir-146a rs2910164, hsa-mir-149 rs2292832, hsa-mir-196a2 rs11614913, and hsa-mir-499 rs3746444) and CRC risk. Methods. We searched PubMed, Web of Knowledge, and CNKI to find relevant studies. The combined odds ratio (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the association in a fixed or random effect model. Results. 15 studies involving 5,486 CRC patients and 7,184 controls were included. Meta-analyses showed that rs3746444 had association with CRC risk in Caucasians (OR = 0.57, 95% CI = 0.34–0.95). In the subgroup analysis, we found significant associations between rs2910164 and CRC in hospital based studies (OR = 1.24, 95% CI = 1.03–1.49). rs2292832 may be a high risk factor of CRC in population based studied (OR = 1.18, 95% CI = 1.08–1.38). Conclusion. This meta-analysis showed that rs2910164 and rs2292832 may increase the risk of CRC. However, rs11614913 polymorphism may reduce the risk of CRC. rs3746444 may have a decreased risk to CRC in Caucasians.

Effect of Proliferator-Activated Receptor-γ Pro12Ala Polymorphism on Colorectal Cancer Risk: A Meta-Analysis.

BackgroundThe association between peroxisome proliferators-activated receptor γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk is still controversial. A meta-analysis was performed.Material/MethodsWe conducted a literature search using PubMed, EMBASE, and Cochran databases. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Fixed-effects and random-effects models were used. Dominant model, recessive model, and additive model were used in this meta-analysis.ResultsFifteen studies including 13575 cases and 17085 controls were included in our meta-analysis. Result of this meta-analysis found that PPARγ Pro12Ala polymorphism was significantly associated with a reduced risk of CRC (OR=0.90; 95% CI 0.83–0.98; P=0.01). No significant association was found between PPARγ Pro12Ala polymorphism and CRC risk in Asians (OR=0.80; 95% CI 0.60–1.09; P=0.15). However, PPARγ Pro12Ala polymorphism was significantly associated with a reduced risk of CRC in Caucasians (OR=0.91; 95% CI 0.83–0.99; P=0.03). When stratified analysis was performed by CRC site, no positive association was found between PPARγ Pro12Ala polymorphism and rectal cancer (OR=0.95; 95% CI 0.74–1.22; P=0.71). However, a reduced risk of colon cancer was observed (OR=0.85; 95% CI 0.76–0.94; P=0.002).ConclusionsIn summary, this study suggests that PPARγ Pro12Ala polymorphism was a protective factor of CRC.

Distinct role of CD86 polymorphisms (rs1129055, rs17281995) in risk of cancer: evidence from a meta-analysis.

Background and PurposePrevious studies concerning the role of CD86 polymorphisms (rs1129055 and rs17281995) in cancer fail to provide compelling evidence. The aim of this study was to investigate the role of common polymorphisms in the risk of cancer by meta-analysis.MethodsBy using the search terms Cluster of Differentiation 86/CD86/B7-2/polymorphism/polymorphisms/cancer, we searched PubMed, Embase, CNKI, and Wanfang and identified four studies for rs1129055 (2137 subjects) and rs17281995 (2856 subjects) respectively. Cancer risk was estimated by odds ratio (OR) and 95% confidence interval (95% CI).Major FindingsOverall, we observed significant reduced risk of cancer in relation to rs1129055. Compared with the individuals with AA genotype, the individuals with GG genotype appeared to have 62% decreased risk to develop cancer (GG versus AA: OR, 0.62; 95% CI, 0.49–0.79; Phet., 0.996). Similar effects were indicated in the G versus A allele model and the GG versus GA+AA genetic model (OR, 0.83; 95% CI, 0.74–0.93; Phet., 0.987; OR, 0.63; 95% CI, 0.50–0.79; Phet., 0.973). In addition, we found genotypes of rs17281995 had a major effect on overall cancer risk (CC versus GG: OR, 2.38; 95% CI, 1.43–3.95; Phet., 0.433; C versus G: OR, 1.23; 95% CI, 1.06–1.43; Phet., 0.521; CC versus GC+GG: OR, 2.38; 95% CI, 1.45–3.93; Phet., 0.443). The association was also observed in Caucasians and colorectal cancer. No obvious publication bias was detected in this meta-analysis.ConclusionsThese data reveal that rs1129055 may have protective effects on cancer risk in Asians and that rs17281995 is likely to contribute to risk of cancer, particularly colorectal cancer in Caucasians.

Mo1138 Socioeconomic Status and Gender Are Associated With Inequalities in Surgical Treatment and Short-Term Outcomes in Patients With Non-Metastatic Colorectal Cancer

effect of race on survival time after adjusting for differences in stage, age and grade using Cox-proportional hazards regression. We used SPSS software (version 19.0) for the analysis. Results: We included 11,184 patients who were less than 50 years (9432 Caucasians and 1752 African-Americans) in our study. The mean (SD) age in years at diagnosis was similar in Caucasians 42(6) and African-Americans 42(6). Sigmoid colon was the commonest site affected in both groups (Caucasians 24% and African-Americans 20%). Differences in tumor characteristics at diagnosis is shown in Table 1. Surgery was performed in most of the patients in both groups (Caucasians 99% and African-Americans 100%). Mean survival was longer in Caucasian patients as compared to African-Americans (15 years vs. 12 years) P , 0.001 Log Rank (Mantel-Cox). Young Caucasians had better 5-year colon cancer-specific survival compared to African-Americans (62% vs. 52% respectively). After adjusting for differences in stage of disease at presentation, age and grade, African-Americans survive shorter time as compared to Caucasians (hazard ratio 95% CI 1.39 (1.28-1.51) (Figure 1). Conclusion: Young African-Americans had advanced stage of colorectal cancer at diagnosis. They had shorter survival time even after adjustment for differences of stage, grade and age. Table1: The characteristics of colorectal cancer in Caucasians and African-Americans

Mo1139 Coffee Consumption Genetic Polymorphisms in CYP1A2 and NAT2, and Colorectal Cancer Risk

effect of race on survival time after adjusting for differences in stage, age and grade using Cox-proportional hazards regression. We used SPSS software (version 19.0) for the analysis. Results: We included 11,184 patients who were less than 50 years (9432 Caucasians and 1752 African-Americans) in our study. The mean (SD) age in years at diagnosis was similar in Caucasians 42(6) and African-Americans 42(6). Sigmoid colon was the commonest site affected in both groups (Caucasians 24% and African-Americans 20%). Differences in tumor characteristics at diagnosis is shown in Table 1. Surgery was performed in most of the patients in both groups (Caucasians 99% and African-Americans 100%). Mean survival was longer in Caucasian patients as compared to African-Americans (15 years vs. 12 years) P , 0.001 Log Rank (Mantel-Cox). Young Caucasians had better 5-year colon cancer-specific survival compared to African-Americans (62% vs. 52% respectively). After adjusting for differences in stage of disease at presentation, age and grade, African-Americans survive shorter time as compared to Caucasians (hazard ratio 95% CI 1.39 (1.28-1.51) (Figure 1). Conclusion: Young African-Americans had advanced stage of colorectal cancer at diagnosis. They had shorter survival time even after adjustment for differences of stage, grade and age. Table1: The characteristics of colorectal cancer in Caucasians and African-Americans

HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis

The HFE gene has been suggested to play an important role in the pathogenesis of colorectal cancer. However, the results have been conflicting. In this study, we performed a meta-analysis to clarify the association of HFE gene C282Y variant with colorectal cancer. PubMed and Embase were retrieved to identify the potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of eight papers including nine studies (7,588 colorectal cancer cases and 81,571 controls) for HFE gene C282Y variant were included in the meta-analysis. The result indicated that HFE gene C282Y variant was significantly associated with colorectal cancer under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis by number of cases suggested the effect was significant in studies with more than 500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %, p = 0.622). The current meta-analysis supported the positive association of HFE gene C282Y variant with colorectal cancer. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

A Functional NQO1 609C&gt;T Polymorphism and Risk of Gastrointestinal Cancers: A Meta-Analysis

BackgroundThe functional polymorphism (rs1800566) in the NQO1 gene, a 609C>T substitution, leading to proline-to-serine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results.Methodology/Principal FindingsWe performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C>T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95% CI = 1.01 – 1.19, P heterogeneity = 0.27, I 2 = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 – 1.20, P heterogeneity = 0.14; I 2 = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies.ConclusionsThis meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyses suggest that further larger studies are needed, especially for non-colorectal GI cancers in Caucasians and GI cancers in Asians.

The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer

Polymorphisms in genes involved in folate metabolism may modulate the risk of colorectal cancer (CRC), but data from published studies are conflicting. The current meta-analysis was performed to address a more accurate estimation. A total of 41 (17,552 cases and 26,238 controls), 24(8,263 cases and 12,033 controls), 12(3,758 cases and 5,646 controls), and 13 (5,511 cases and 7,265 controls) studies were finally included for the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1289C, methione synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G polymorphisms and the risk of CRC, respectively. The data showed that the MTHFR 677T allele was significantly associated with reduced risk of CRC (OR = 0.93, 95%CI 0.90-0.96), while the MTRR 66G allele was significantly associated with increased risk of CRC (OR = 1.11, 95%CI 1.01-1.18). Sub-group analysis by ethnicity revealed that MTHFR C677T polymorphism was significantly associated with reduced risk of CRC in Asians (OR = 0.80, 95%CI 0.72-0.89) and Caucasians (OR = 0.84, 95%CI 0.76-0.93) in recessive genetic model, while the MTRR 66GG genotype was found to significantly increase the risk of CRC in Caucasians (GG vs. AA: OR = 1.18, 95%CI 1.03-1.36). No significant association was found between MTHFR A1298C and MTR A2756G polymorphisms and the risk of CRC. Cumulative meta-analysis showed no particular time trend existed in the summary estimate. Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test. Collectively, this meta-analysis suggested that MTHFR 677T allele might provide protection against CRC in worldwide populations, while MTRR 66G allele might increase the risk of CRC in Caucasians. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.

Contribution of NAD(P)H Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and Risk of Colorectal Adenoma and Colorectal Cancer in Caucasians: A Meta-analysis

The effects of polymorphism of NAD(P)H quinone oxidoreductase 1 (NQO1 Pro187Ser, rs1800566) on the risks of colorectal adenoma and cancer have been widely studied and results remain controversial. Therefore, the aim of this meta-analysis was to quantitatively assess the relationships. Databases of Medline, Embase and Wanfang were retrieved until May 15, 2011. Pooled odds ratio (OR) and 95% confidence interval (95% CI) as effect sizes were calculated by using fixed- or random-effect model. Cochrane Q-test was used to explore between-study heterogeneity; p <0.10 indicated statistical significance. A total of 12 case-control studies with 11,700 individuals (including 5528 cases and 6172 controls) were included in this meta-analysis. Of these studies, four studies conducted in Caucasian populations were for colorectal adenoma, and eight studies were for colorectal cancer. NQO1 187Ser allele was significantly associated with increased risk of colorectal adenoma in co-dominant and dominant comparison models (OR = 1.07, 95% CI = 1.04-1.32 for ProSer vs. ProPro and OR = 1.19, 95% CI = 1.06-1.33 for Ser carries vs. ProPro), without between-study heterogeneity. Overall, NQO1 Pro187Ser was not associated with risk of colorectal cancer, without between-study heterogeneity. Subgroup analyses indicated that Ser allele was significantly associated with increased risk of colorectal cancer for Caucasians (OR = 1.14, 95% CI = 1.00-1.30 for ProSer vs. ProPro and OR = 1.16, 95% CI = 1.02-1.31 for Ser carries vs. ProPro). This meta-analysis suggested that Ser allele of NQO1 Pro187Ser significantly contributed to the increased risks of colorectal adenoma and cancer in Caucasians.

Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians

Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene-environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians.

CYP2E1 PstI/RsaI polymorphism and colorectal cancer risk: A meta-analysis

To clarify the association between CYP2E1 PstI/RsaI polymorphism and susceptibility to colorectal cancer. A meta-analysis based on 10 eligible case-control studies involving 4979 cases and 6012 controls was carried out to summarize the data on the association between CYP2E1 RsaI/PstI polymorphism and colorectal cancer risk. In comparison of the homozygote c2c2 and c2 carriers (c1c2 + c2c2) and the homozygous wild-type genotype (c1c1), no association was found between CYP2E1 RsaI/PstI polymorphism and colorectal cancer risk [odds ratio (OR) = 1.24 (95% CI: 0.93-1.66) for c2c2; OR = 1.02 (95% CI: 0.88-1.19) for c2 carriers]. In stratified analysis, Caucasians with c2c2 homozygote appeared to have an increased risk of colorectal cancer (OR = 2.67, 95% CI: 1.03-6.89, P = 0.043), no significant associations were found in other groups. c2c2 homozygote of CYP2E1 PstI/RsaI polymorphism may be associated with the increased risk of colorectal cancer in Caucasians, which needs further investigations.

Vitamin D receptor haplotypes protect against development of colorectal cancer

We investigated the association of vitamin D receptor polymorphisms and colorectal cancer incidence in a Caucasian population. Frequencies of the vitamin D receptor gene polymorphisms 23005G>A (CDX-2), 27823C>T (FokI), 60890G>A (BsmI), 61050G>A (Tru9I), 61888G>T (ApaI), and 61968T>C (TaqI) were determined in a series of 256 colorectal cancer patients and 256 patients without malignant disease (case-control study) using polymerase chain reaction and restriction fragment length polymorphism genotyping assays (PCR-RFLP). Haplotype analysis based on the six genetic loci was applied to the received genotypes. Pairwise linkage disequilibrium between BsmI, ApaI, TaqI, and Tru9I was confirmed (P < 0.001). Allele frequencies did not differ between the groups. There was no association between any single variant and colorectal cancer. However, haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) were inversely associated with colorectal cancer incidence (P < 0.001), the odds being 15.0 times smaller [odds ratio (OR) 0.067; 95% confidence interval (CI), 0.016-0.284] and 5.3 times smaller (OR 0.188; 95% CI 0.077-0.461), respectively, compared with noncarriers. Our findings suggest that vitamin D receptor haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) have a protective effect against colorectal cancer in Caucasians.