No association between the polymorphisms in CDX2 coding regions and colorectal cancer in Chinese

CDX2 has been shown to play an important role in the pathogenesis of colorectal cancer. The aim of this study was to investigate whether genetic variants in CDX2 contributed to the development and progression of colorectal cancer in a Chinese population. We detected the polymorphisms in the CDX2 coding regions in 126 patients with colorectal cancer and matched tumor-free subjects by PCR-based DHPLC. The correlation between the genotypes and clinicopathological parameters among colorectal cancer cases was also investigated. Three SNPs were identified in the coding region of the CDX2 gene. Neither the genotype frequencies nor allele frequencies of CDX2 polymorphisms showed significant difference from those in healthy controls. There were also no significant association between genotypes and clinicopathological features. When we examined the linkage disequilibrium between three SNPs using expectation-maximization algorithm, we found that there is strong linkage disequilibrium among these SNPs, but no significant difference was found in haplotypes distribution. Our present data suggest that the CDX2 polymorphisms may not be used as a useful marker to predicate susceptibility of colorectal cancer in Chinese.     

No association of XRCC1 polymorphisms Arg194Trp and Arg399Gln with colorectal cancer risk

Background: X-ray repair cross complementation group 1 (XRCC1) plays a key role in base excision repair. The purpose of this study was to examine the association of two genetic polymorphisms in XRCC1 (rs1799782 and rs25487) with risk of colorectal polyps and colorectal cancer (CRC). Methods: In the ongoing colorectal cancer study of Austria (CORSA), a total of 3091 Caucasian participants was genotyped using 5′-nuclease TaqMan assays. Multiple logistic regression was applied to compare individuals of the control group against three different case groups namely CRC cases, high-risk and low-risk polyps. Results: The two investigated SNPs in XRCC1 were not found to be associated with neither CRC risk nor polyp risk. Comparing the CRC cases versus the controls the OR was 0.60 (95%CI 0.27–1.31) for the heterozygous polymorphic genotype of SNP rs1799782 and 1.47 (95%CI 0.81–2.65) for the homozygous polymorphic genotype of SNP rs25487. Comparing the high-risk polyp group versus the controls the OR was 2.64 (95%CI 0.61–11.42) for the homozygous polymorphic genotype of SNP rs1799782 and 0.89 (95%CI 0.60–1.33) for SNP rs25487, respectively. In an haplotype analysis also no statistically significant association was found. Conclusion: Our finding that none of the two investigated SNPs of XRCC1 were significantly associated with risk of CRC or polyps is consistent with the results of a recently published meta-analysis.     

Meta-analysis of new genome-wide association studies of colorectal cancer risk

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8?×?10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p?相似文献   

Interactions between meat intake and genetic variation in relation to colorectal cancer

Meat intake is associated with the risk of colorectal cancer. The objective of this systematic review was to evaluate interactions between meat intake and genetic variation in order to identify biological pathways involved in meat carcinogenesis. We performed a literature search of PubMed and Embase using “interaction”, “meat”, “polymorphisms”, and “colorectal cancer”, and data on meat–gene interactions were extracted. The studies were divided according to whether information on meat intake was collected prospectively or retrospectively. In prospective studies, interactions between meat intake and polymorphisms in PTGS2 (encoding COX-2), ABCB1, IL10, NFKB1, MSH3, XPC (P_int = 0.006, 0.01, 0.04, 0.03, 0.002, 0.01, respectively), but not IL1B, HMOX1, ABCC2, ABCG2, NR1I2 (encoding PXR), NR1H2 (encoding LXR), NAT1, NAT2, MSH6, or MLH1 in relation to CRC were found. Interaction between a polymorphism in XPC and meat was found in one prospective and one case–control study; however, the directions of the risk estimates were opposite. Thus, none of the findings were replicated. The results from this systematic review suggest that genetic variation in the inflammatory response and DNA repair pathway is involved in meat-related colorectal carcinogenesis, whereas no support for the involvement of heme and iron from meat or cooking mutagens was found. Further studies assessing interactions between meat intake and genetic variation in relation to CRC in large well-characterised prospective cohorts with relevant meat exposure are warranted.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0448-9) contains supplementary material, which is available to authorized users.     

The association between three AXIN2 variants and cancer risk

Plenty of epidemiological studies have assessed the effects of AXIN2 polymorphisms on the risk of developing cancer, but the available results were somewhat inconclusive. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the relationship between three AXIN2 variants (rs2240308 C/T, rs1133683 C/T, and rs4791171 A/G) and overall cancer susceptibility. In silico tools were undertaken to investigate the correlation of AXIN2 expression with cancer risk and survival time. Furthermore, we explored the serum expression of AXIN2 by enzyme-linked immunosorbent assay. A total of 4167 cancer patients and 3515 control subjects were evaluated. The overall results demonstrated that there was no major association of these polymorphisms on cancer risk. However, stratified analysis by cancer type showed evidence that rs2240308 C/T polymorphism had a lower risk in lung cancer (OR, 0.76; 95% CI, 0.63-0.92; P_{heterogeneity} = 0.865) and prostate cancer (OR, 0.54; 95% CI, 0.35-0.84; P_{heterogeneity} = 0.088) by heterozygote comparison. Similar results were indicated in Asian descendants and population-based studies. In silico analysis showed evidence that AXIN2 expressions in lung cancer and prostate cancer were lower than that in normal counterpart. High expression of AXIN2 may have longer overall survival time than low expression group for lung cancer participants. In addition, individuals who were CC/TC carriers had a higher serum expression level than TT carriers. In conclusion, this pooled analysis suggested that AXIN2 rs2240308 C/T variant may decrease both lung and prostate cancer susceptibility, particularly in Asian descendants and population-based studies. Future large scale and well-designed research are required to validate these effects in more detail.     

The association of polymorphisms on TGFBR1 and colorectal cancer risk: a meta-analysis

Epidemiological studies found inconsistent results on the association of two variants on TGFBR1 (TGFBR1*6A and Int7G24A) with colorectal cancer (CRC) risk. The present study was aimed to evaluate the association of these two variants with CRC susceptibility via the meta-analysis methods. For variant TGFBR1*6A, nine reports including 6,765 CRC patients and 8,496 unrelated controls were identified. The heterozygotes *6A/*9A showed a significant increased risk of CRC with the pooled OR was 1.12 (95% CI = 1.02–1.23), and the pooled OR for the homozygotes *6A/*6A was 1.13 (95% CI = 0.80–1.58) compared to the homozygotes *9A/*9A. However, under the dominant effect model, the TGFBR1*6A carriers showed a significantly increased CRC risk (pooled OR = 1.12, 95% CI = 1.03–1.23, *6A/*6A and *6A/*9A vs. *9A/*9A). For variant Int7G24A, three case–control studies with 1,074 cases and 1,945 controls were found. Although no significant association was found for heterozygosity Int7G24A carriers with CRC risk (pooled OR = 0.97, 95% CI = 0.67–1.42), the homozygosity A/A carriers showed a significant elevated risk of CRC (pooled OR = 1.68, 95% CI = 1.14–2.47) compared to G/G homozygotes. Under the recessive effect model, homozygotes A/A showed a 71% increase of CRC risk compared to the A/G and G/G genotype carriers (pooled OR = 1.71, 95% CI = 1.17–2.51). These data strongly suggested that the two polymorphisms of TGFBR1 may confer low-penetrance susceptibility of CRC risk.     

Folate intake and bowel cancer risk

Folate is a B vitamin required for one-carbon transfer reactions including methylation of cell macromolecules including DNA and synthesis of the purines adenosine and guanosine and the pyrimidine thymidine. Epidemiological evidence suggests that diets providing higher amounts of folates lower the risk of colo-rectal cancer (CRC) and these observations are supported by plausible biological mechanisms. Inadequate folate supply results in DNA damage through (a) the incorporation of uracil (in place of thymidine) into DNA and subsequent unsuccessful attempts at DNA repair and (b) aberrant patterns of DNA methylation. However, human intervention studies using relatively large doses (500–5,000 μg/day) of folic acid (a synthetic form of folate) have provided no evidence of benefit in terms of adenoma recurrence. Indeed, there is some evidence of potential harm in increased risk of prostate cancer. Possible reasons for the apparent divergence in findings from the observational and intervention studies include the use of (unphysiologically) large doses of folic acid in the intervention studies whereas smaller intakes of food folates appeared to offer “protection” against CRC in case–control and prospective cohort studies. With intakes of folic acid greater than 400 μg/day, unmetabolised folic acid appears in peripheral blood and there are suggestions that this folic acid may have adverse effects e.g. reduced cytotoxicity of Natural Killer cells. Until the benefit-risk relationship associated with mandatory fortification with folic acid has been clarified (and, in particular, the possible risk of inducing extra cases of bowel or other cancer), it would seem wise to delay further mandatory folic acid fortification.     

Meta-analysis of association between cytokine gene polymorphisms and lung cancer risk

The aim of this study was to evaluate the association between various cytokine gene polymorphisms and lung cancer (LC) susceptibility. We searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. Totally, 20 studies involving 6,467 cases and 8,320 controls were included in the meta-analysis. The effects of eight polymorphisms, i.e. TNF-α 308G/A, IL-6 174G/C, IL-1β 31T/C, IL-1β 511C/T, COX-2 8473T/C, IL-10 1082G/A, IL-10 819C/T, and IL-10 592C/A were evaluated. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between IL-10 polymorphism and LC. For IL-10 1082G/A, the overall ORs (95% CI) of the G versus A, GG versus AA, and GG/GA versus AA were 2.35 (1.16–4.76), 2.07 (1.16–3.70) and 3.17 (1.31–7.68), respectively. For IL-10 819C/T, the pooled ORs (95% CI) of the C versus T and CC versus TT were 1.27 (1.01–1.58) and 2.27 (1.32–3.89). For IL-10 592C/A, the comparison of subjects in the CC or CC/CA genotype versus AA homozygotes showed significant results (OR = 2.00, 95% CI: 1.24–3.23; OR = 1.80, 95% CI: 1.28–2.54). But, other gene polymorphisms did not reach statistical associations. IL-10 1082G/A, 819C/T and 592C/A polymorphisms might be risk factors for LC. TNF-α 308G/A, IL-6 174G/C, IL-1β 31T/C, IL-1β 511C/T, COX-2 8473T/C polymorphisms were not detected to be related to the risk for LC. Due to the limitation of the number of the studies, we should take the conclusion with caution. While, further studies are necessary for more precise association.     

No association between methylenetetrahydrofolate reductase C677T polymorphism and breast cancer

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme (EC 1.5.1.20), that reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a carbon donor for the homocysteine to methionine conversion. MTHFR is a key enzyme that regulates folate metabolism which has an important role in DNA synthesis, DNA repair and methylation. The association between MTHFR C677T polymorphism and breast cancer has been investigated in several previous studies. Some researchers have shown an association between C677T polymorphism and breast cancer, but not all researchers found this association however. This study was designed to investigate, in the Turkish population, the association of MTHFR C677T polymorphism and breast cancer. Forty women patients with breast cancer and 68 healthy women were included in the study. MTHFR gene polymorphism was determined by the PCR-RFLP method. SPSS 10.0 for windows was used to determine statistical significance. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in the cases versus the controls. It was found that the frequencies of MTHFR polymorphism were 55%, 40%, 5% for CC, CT, TT genotype in patients and 56%, 38%, 6% in healthy controls respectively. Furthermore, association was observed among family history, metastatic risk and MTHFR genotypes in patients. Our data fail to support a relationship between MTHFR C677T and the risk for breast cancer. It may be that there are ethnic differences in terms of this relationship.     

The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk

This study aimed to determine the relation between methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism and lung cancer risk and the frequency of this polymorphism. The study involved 64 lung cancer patients (the study group) with definitive diagnosis and 61 noncancerous subjects (the control group). MTHFR C677T and A1298C mutation analysis was made using DNA isolated from peripheric blood and multiplex PCR and reverse hybridization strip test. Eighty-four percent of the patients were male. The age, gender, and history of alcohol use of the patients and control group were statistically similar. While MTHFR 677T and 677C allele frequency was 0.33 and 0.67 in the patients respectively, it was 0.29 and 0.71 in the control group. The frequencies of MTHFR 1298C and 1298A were 0.33 and 0.67 in the patients, and it was 0.31 and 0.69 in the control group respectively. When MTHFR 677TT and 677CT genotypes were compared with 677CC genotype, lung cancer risk was 2.4 times higher in the 677TT genotype. When MTHFR 1298AC and 1298CC genotypes were compared with 1298AA genotype, lung cancer risk was 1.5 times higher in 1298CC genotype. According to the results, allele frequency of homozygote T and C was high in lung cancer patients. It was 3.05 and 1.29 times higher in smokers than in non-smokers, and 3.05 and 1.64 times higher in males than in females; 3.0 and 2.44 times higher in those with non-small cell lung cancer than in those with small-cell lung cancer.     

An association between NQO1 genetic polymorphism and risk of bladder cancer

NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that plays a critical role in protecting cells against chemically induced oxidative stress, cytotoxicity, mutagenicity, and carcinogenicity. NQO1 protects cells from oxidative damage by preventing the generation of reactive oxygen species and reducing certain environmental carcinogens, such as nitroaromatic compounds, heterocyclic amines, and possible cigarette smoke condensate. A C-->T single nucleotide polymorphism in exon 6 was shown to reduce NQO1 enzyme activity, which may diminish the protection provided by NQO1. Therefore, we hypothesized that people with the variant allele genotypes of NQO1 are at higher risk for bladder cancer. In an ongoing case-control study, the NQO1 genotypes were successfully identified by polymerase chain reaction restriction fragment length polymorphism in 265 bladder cancer patients and 261 control subjects matched for age, sex, and ethnicity. The frequency of the variant NQO1 allele was 18% for controls and 21% for cases. The variant allele genotypes of NQO1 were associated with a higher risk of bladder cancer in Caucasians (odds ratio (OR)=1.51; 95% confidence interval (CI)=1.01-2.25). Further analysis in Caucasians showed an elevated bladder cancer risk in men (OR=1.75; 95% CI=1.08-2.85) but not in women (OR=1.16; 95% CI=0.57-2.37). In addition, the variant allele genotypes were associated with higher bladder cancer risk in ever smokers (OR=1.78; 95% CI=1.06-3.00), but not in never smokers (OR=1.19; 95% CI=0.65-2.20). These results suggest that the NQO1 genetic polymorphism modulates bladder cancer risk, especially in men and ever smokers.     

No association between Parachlamydia infection and atherosclerosis

Since recent studies suggested a role for Parachlamydia in atherosclerosis, we investigated 354 patients with or without atherosclerosis for Parachlamydia infection. Six patients exhibited anti- Parachlamydia IgG. No patient presented IgM. Parachlamydial DNA was not amplified from peripheral blood mononuclear cells. There was no association between atherosclerosis and Parachlamydia infection.     

Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer

Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10-15% risk of ovarian cancer. The perceived risk among mutation carriers may, however, deviate from the risk communicated and has been demonstrated to influence adherence to control programs. We investigated the perceived cancer risk among HNPCC mutation carriers (n = 47) and correlated the findings to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1 year prior to the study reported higher, albeit not significantly, perceived risks of colorectal cancer. Higher perceived risks were also reported by individuals who had lost a parent to HNPCC-related cancer at early age, whereas individuals with a personal history of cancer did not report a higher perceived risk. Regarding gynecological cancer, 6/18 females reported a perceived risk of 40-60% for endometrial cancer, whereas the remaining women both underestimated and overestimated their risk, and none of the women referred to the risk of ovarian cancer. We conclude that despite educational efforts and an increasing amount of data on the cancer risk in HNPCC, a minority of the mutation carriers report a perceived risk at the same level as that communicated during oncogenetic counseling.     

The association between KL polymorphism and prostate cancer risk in Korean patients

The Klotho (KL) gene is a classical “aging suppressor” gene. Although recent studies have shown that KL participates in the progression of several types of human cancers, the relationship between KL polymorphism and prostate cancer was unknown. The present study aimed to investigate the association between KL genetic polymorphisms and prostate cancer. Twenty-five common single nucleotide polymorphisms (SNPs) in KL gene (including KL gene polymorphism C1818T in exon 4) were assessed in 272 prostate cancer cases and 173 controls. Single-locus analyses were conducted using unconditional logistic regression. In addition, we did a haplotype analysis for the 25 KL SNPs tested. CC genotype of C1548T KL polymorphism had approximately twofold increased prostate cancer risk compared with the homozygous genotype TT and heterozygote CT (odds ratio 1.85 [95 % CI, 1.09–3.12], P = 0.02). We also found that non-T allele carriers had significantly higher prostate cancer risk associated with the prostate cancer clinical characteristics (tumor stage or Gleason score). Our findings suggested that the C1548T polymorphism of KL gene is associated with the prostate cancer and may act as a risk factor for the development of prostate cancer.     

No association between XRCC1 genetic polymorphisms and differentiated thyroid carcinoma risk: a meta-analysis

The X-ray repair cross-complementing group 1 (XRCC1) gene belongs to the family of DNA repair genes. Polymorphisms in the XRCC1 gene, Arg399Gln, Arg194Trp and Arg280His, have been reported to have implications in differentiated thyroid carcinoma (DTC) susceptibility, but the results remain conflicting and no meta-analysis has been published. Therefore, we carried out a systematic review of the published epidemiology studies, aiming to assess the relationship between XRCC1 polymorphisms and susceptibility to DTC risk. We selected three databases, PubMed, EMBASE and CNKI, in which to search for published literature. With respect to DTC risk associated with XRCC1, combined odds ratios (ORs) and 95 % confidence intervals (CI) were appropriately calculated on the basis of co-dominant, dominant and recessive models. To investigate different effects from specific race, subgroup analyses were carried out in Asian and Caucasian populations. Eight studies meeting the inclusion criteria were eventually selected for Arg399Gln (1,550 cases and 2,692 controls), five studies for Arg194Trp (858 cases and 1,394 controls) and five studies for Arg280His (1,237 cases and 2,267 controls). The combined results of the relevant studies exhibited that no significant associations with DTC risk were demonstrated for polymorphisms in XRCC1 Arg399Gln, Arg194Trp and Arg280His in all genetic models. Stratified analyses in Asian and Caucasian populations showed similar results. This meta-analysis arrives at a conclusion that the XRCC1 (Arg399Gln, Arg194Trp, Arg280His) polymorphisms appear to confer no risk for DTC.     

The association of garlic with Helicobacter pylori infection and gastric cancer risk: A systematic review and meta‐analysis

Background

Garlic may be protective against Helicobacter pylori infection and gastric cancer development. We conducted this study to quantitatively update evidence on garlic intake and gastric cancer with the inclusion of most recent cohort studies and qualitatively summarize epidemiological studies of garlic consumption and Helicobacter pylori infection.

Materials and Methods

PubMed, Embase, MEDLINE, and Cochrane Library were searched on April 2018. We conducted a meta‐analysis to determine whether garlic intake reduced gastric cancer risk using random‐effect models and a systematic review to summarize evidence on the association between garlic consumption and Helicobacter pylori infection. Risk of bias was assessed using tools of Cochrane risk of bias and Robins‐I for randomized and nonrandomized studies, respectively.

Results

Meta‐analysis of 18 studies (142 921 subjects) demonstrated high garlic consumption (as comparing the highest category to the lowest) was associated with a reduced gastric cancer risk (OR = 0.51, 95% CI = 0.44‐0.57). This association became nonsignificant if only derived from the prospective studies (OR = 0.95, 95% CI = 0.66‐1.24). Thirteen studies (4889 participants) were included in the systematic review for garlic consumption and Helicobacter pylori infection; ten of which found no significant results. The majority of these studies were poor in quality given the small sample size and high risk of bias.

Conclusions

Pooled evidence, mainly from case‐control studies, suggested a significant inverse association of garlic intake with gastric cancer risk. Given the limitations of included studies, current epidemiological evidence is not sufficient to reach any definite conclusion regarding the association of garlic with Helicobacter pylori infection.     

No association of PTPN1 polymorphisms with macronutrient intake and measures of adiposity

The protein tyrosine phosphatase nonreceptor type1 (PTPN1) gene encodes for the protein tyrosine phosphatase 1B, which suppresses the signaling pathway of leptin. Variations of the PTPN1 gene may lead to changes in leptin sensitivity and thereby influence eating behavior and measures of obesity. This study investigated the association between single-nucleotide polymorphisms (SNPs) of the PTPN1 gene and eating behavior and different measures of obesity, including visceral fat. We used data from a population-based, cross-sectional study of 382 Dutch white men aged 40-80 years. Self-reported macronutrient intake was collected with a food frequency questionnaire. Anthropometrical measurements included BMI, waist and hip circumference, total lean and fat mass measured with dual-energy X-ray absorptiometry, and visceral and subcutaneous fat measured with ultrasound. Associations were studied using linear regression analysis. There were no statistically significant associations of SNPs in the PTPN1 gene with dietary phenotypes or measures of obesity.