HDL-C, longitudinal change and risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: High-density lipoprotein cholesterol (HDL-C) concentration and variability are both important factors of cardiovascular disease (CVD) and mortality. We aimed to explore the associations of HDL-C and longitudinal change in HDL-C with risk of mortality. METHODS AND RESULTS: We recruited a total of 69,163 participants aged ≥40 years and had medical examination records of HDL-C during 2010-2014 from the Yinzhou District, Ningbo, China. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. We observed a non-linear association of HDL-C with risks of non-accidental and CVD mortality. Compared with the moderate concentration group (1.4-1.6 mmol/L), HDL-C <1 mmol/L was associated with a higher risk of non-accidental mortality (HR: 1.13 (95% CI: 1.01-1.27)) and both HDL-C <1 mmol/L and ≥2 mmol/L were associated with a higher risk of CVD mortality (HRs: 1.23 (95% CI: 1.01-1.50) and 1.37 (95% CI: 1.03-1.82), respectively). Compared with the stable group ([-0.1, +0.1 mmol/L]), a large decrease ([-0.5, -0.3 mmol/L]) and very large decrease (<-0.5 mmol/L) in HDL-C were associated with a higher risk of non-accidental mortality (HRs: 1.40 (95% CI: 1.21-1.63) and 1.78 (95% CI: 1.44-2.20), respectively). Similar results were observed for CVD mortality and cancer mortality. CONCLUSION: Extremely low or high HDL-C and a large decrease or very large decrease in HDL-C were associated with a higher risk of cause-specific mortality. Monitoring of HDL-C may have utility in identifying individuals at higher risk of mortality.

Low LDL-C levels are associated with risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data. METHODS: We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100-130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80-3.53), CVD (HR = 1.84, 95% CI: 1.28-2.61), ischemic stroke (HR = 2.29, 95% CI:1.32-3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57-7.85), and cancer (HR = 2.12, 95% CI: 1.04-4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1. CONCLUSIONS: Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.

Association between CPR-related genetic variants and risk of ischemic stroke: a nested case-control study.

Background: Serum C-reactive protein (CRP) has been reported to be associated with risk of ischemic vascular disease including ischemic stroke. Genome-wide association studies have revealed several gene variants related to CRP concentration. Methods: We investigated genetic variants in CRP-related genes associated with ischemic stroke in a nested case-control study with 138 ischemic stroke cases and 276 controls. We sequenced the whole coding region of six CPR-related genes and selected eligible SNPs. Three genetic models (additive, dominant and recessive) were calculated by a multivariable conditional logistic regression to estimate the association between SNPs and risk of ischemic stroke. We also calculated gene-environment interactions by using a crossover analysis. Results: Three out of 10 eligible SNPs were shown to be associated with risk of ischemic stroke. rs1800947 in CRP gene (additive model: OR = 2.08, 95% CI: 1.00-4.23) and rs1169288 in HNF1A gene (additive model: OR = 1.45, 95% CI: 1.03-2.06) were associated with an increased risk of ischemic stroke. rs440446 in APOE gene (additive model: OR = 0.63, 95%CI: 0.44-0.88) was associated with a decreased risk of ischemic stroke. Genetic risk scores models including SC-GRS and OR-GRS both showed a significant association with risk of ischemic stroke. These three SNPs interacted with smoking and red meat intake. Conclusions: Our study showed genetic variants of CRP-related genes were associated with risk of ischemic stroke. Our findings could provide useful data for the etiology of ischemic stroke.

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.

Association of a pre-miR-27a polymorphism with cancer risk: an updated meta-analysis.

MicroRNA-27a is highly expressed in cancers and has been identified as an oncogenic microRNA. A genetic variant in pre-miR-27a (rs895819) with a transition of A to G has been demonstrated to be associated with cancer risk; however, the results of these studies remain conflicting rather than conclusive. Therefore, we performed a meta-analysis to derive a more precise estimation. Through searching PubMed or other databases up to March 2014 using the following MeSH terms and keywords, "miR-27a", "polymorphism" and "cancer", seventeen case-control studies were identified in this meta-analysis, including 7,813 cases and 9,602. Crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to investigate the association strength between rs895819 and the susceptibility of cancer. The results of the overall meta-analysis did not suggest any association between rs895819 polymorphism and cancer susceptibility, and this remained in Asians as a sub- group. In Caucasians, however, the rs895819 was associated with a reduced cancer risk in heterozygous (OR, 0.83; 95%CI, 0.75-0.93) and dominant models (OR, 0.84; 95%CI, 0.76-0.93), and the [G] allele of rs895819 showed a protective effect (OR, 0.90, 95%CI, 0.84-0.97). Further studies showed a significant association between the [G] allele of rs895819 and decreased risk of breast cancer (0.91; 95%CI, 0.85-0.98), and stratified analyses indicated a protective effect of the [G] allele in Caucasians (OR, 0.89; 95%CI, 0.82-0.98), younger breast cancer cases (OR, 0.87; 95%CI, 0.79-0.96), and in the group of unilateral breast cancer patients (OR, 0.90; 95%CI, 0.83-0.97). These findings suggest an association between pre-miR-27a polymorphism rs895819 and cancer risk in Caucasians. The protective effect of rs895819 [G] allele in younger breast cancer and in the group of unilateral breast cancer patients await further confirmation since the included studies in this meta-analysis were limited.

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.

RPSA gene mutants associated with risk of colorectal cancer among the chinese population.

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) in ribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and 387 patients with CRC was conducted in a Chinese population. Information about socio-demography and living behavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291) in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotype had a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustment for covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00). Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Among the subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC (OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects in comparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibility to CRC and influence the protective effect of tea consumption in the Chinese population.

[Association between H-ras and L-myc gene polymorphisms and susceptibility to colorectal cancer].

OBJECTIVE: To explore the association between the polymorphisms of oncogenes H-ras and L-myc and colorectal cancer risk, and the interaction of those genes. METHODS: The genotypes of H-ras and L-myc genes were determined by polymerase chain reaction-based restriction fragment length polymorphism analysis. Stratified analysis and logistic model were used to detect the gene-gene interaction. The gene-gene interaction was validated by multifactor dimensionality reduction (MDR) analysis. RESULTS: The single SNP model showed that the polymorphisms of H-ras and L-myc genes were not significantly related with colorectal cancer risk (P > 0.05). Stratified analysis revealed that among the L-myc LS + SS genotype carriers, those with H-ras TC + CC genotype showed significantly increased risk of rectal cancer than those with TT genotype (OR = 1.81, P = 0.005). The positive interaction between L-myc and H-ras was detected by logistic regression model. The OR of the interaction effect was 2.74 (P = 0.024). This result was confirmed in the MDR model, with 54.83% testing balanced accuracy and 10/10 cross-validation consistency, and the model was still significant after the 1000 times permutation test (P = 0.001). CONCLUSION: Our findings suggest that the polymorphism of H-ras and L-myc genes is not related to colorectal cancer risk, but there is a synergy between H-ras and L-myc polymorphisms in the development of rectal cancer.

[Association of CASP3 and CASP9 polymorphisms with genetic susceptibility to stomach cancer].

OBJECTIVE: To investigate the association between the apoptosis genes CASP3(rs12108497) and CASP9 (rs4646018) polymorphisms and the risk of developing stomach cancer. METHODS: In this population-based case-controlstudy, 278 cases with stomach cancer and 278 age (± 5 years), gender, and residential area matched controls were recruited. The genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The unconditional Logistic regression analysis was utilized to calculate the odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The individuals with TC, CC genotypes of rs12108497 locus had significantly increased risk of stomach cancer in comparison to those carrying TT genotype (OR= 1.45, 95% CI: 1.01-2.07 for TC; OR= 2.17, 95%CI: 1.15-4.08 for CC). However, the rs4646018 locus of CASP9 gene polymorphism was not related to stomach cancer risk. Compared with the subjects carrying the both low-risk genotypes, those carrying 1 or 2 high-risk genotypes had a noteworthy increased risk of stomach cancer (OR= 1.60, 95% CI: 1.12-2.30). The combined high-risk genotypes appeared to be more evident in subjects of male (OR= 1.62, 95% CI: 1.05-2.49), ever-smokers (OR= 1.87, 95%CI: 1.12-3.12), ever-drinkers (OR= 1.92, 95%CI: 1.02-3.65) and no family history of cancer (OR= 1.78, 95%CI: 1.18-2.68). CONCLUSION: The current findings suggest that the polymorphism of CASP3 rs12108497 might be associated with the risk of stomach cancer. However, the CASP9 rs4646018 polymorphism may not be related to the stomach cancer risk.

[Expression of caspase apoptosis pathway genes mRNA in colorectal cancer and polyps].

OBJECTIVE: To investigate mRNA expression of caspase apoptosis pathway genes in colorectal cancer, polyps and normal mucosa. METHODS: Nineteen patients with colorectal cancer, 86 patients with polyps and 10 normal controls were enrolled from 2008 to 2010. Fluorescence quantitative RT-PCR was performed to detect the mRNA expression of caspase apoptosis pathway genes (caspase-2,-3,-6,-7,-8,-9 and -10) in colorectal cancer, polyps and normal mucosa. RESULT: There were no statistically significant differences of demographic characteristics between patients with colorectal cancer, patients with polyps and normal controls. Compared with normal control group, the mRNA expression of all selected genes except for caspase-3 were lower; however, the P values did not reach statistic significance. Highly positive correlations were observed between mRNA expression of all selected genes except caspase-9. CONCLUSION: There are no significant changes in mRNA expression levels of caspase apoptosis pathway genes from normal mucosa to polyps to cancer. The mRNA expressions of most caspase pathway genes are highly correlated with each other.

[Association of CASP3 polymorphisms and its haplotypes with susceptibility of breast cancer].

OBJECTIVE: To investigate the association of Caspase3 (CASP3) polymorphisms with susceptibility of breast cancer in Chinese Han population. METHODS: In this population-based case-control study, 251 cases with breast cancers and 251 matched controls in terms of habitation and age (±5 years) were recruited. Rs4647693, rs2696056, rs4647610 were selected as TagSNPs in CASP3 gene and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The haplotype distribution was estimated and compared by PHASE software. RESULT: There was significant association between menarche age and breast cancer (P=0.007), as well as the early pregnancy age and breast cancer (P=0.002). No significant differences were detected in the distribution of CASP3 genotype and haplotype frequencies between breast cancer patients and controls. The GGA was the most common haplotype both in cases and controls. CONCLUSION: CASP3 polymorphisms and its haplotypes were not related to the susceptibility of breast cancer.

[Association of miR-605 and miR-149 genetic polymorphisms with related risk factors of lung cancer susceptibility].

OBJECTIVE: To explore association of miR-149 and miR-605 polymorphisms with other risk factors of lung cancer susceptibility among Chinese population. METHODS: Two hundred and forty-four patients with lung cancer and 243 cancer-free controls matched by age and sex were enrolled from 2002 to 2008. Peripheral venous blood samples were collected from all subjects. Single nucleotide polymorphisms (SNPs) of miR-149 and miR-605 were genotyped by PCR-RFLP. Multiple-variable logistic regression model was used to assess the association of SNPs and cancer related risk factors for lung cancer. RESULT: There was not significant association of SNPs of miR-149 and miR-605 with lung cancer. A marginal significance was observed while the males with at least one G allele of miR-605 had higher risk of lung cancer (OR=1.5, 95% CI:1.0-2.3) than those with AA genotype. Increased frequency of smoking was associated with lung cancer risk. Compared with no-smoker, the subjects with <20 and >20 cigarettes/day had higher risk of lung cancer: OR (95%CI)=1.7(1.0-3.0) for <20 cigarettes, OR (95%CI)=4.2(2.3-7.6) for >20 cigarettes. There was no interaction between two genes and smoking on lung cancer. CONCLUSION: miR-149 polymorphisms may not affect lung cancer susceptibility. miR-605 gene mutant might be increase the risk of lung cancer among males. Cigarette smoking increased a risk of lung cancer, but there were not interactive effects between two gene and smoking on lung cancer.

[Application of flexible matching strategy to detect gene-environment interactions for increasing the study power].

INTRODUCTION: Flexible matching has recently been proposed as a method of improving interactions efficiency. In this study, the concept of flexible matching has been introduced, and the applicability of this strategy has also been described based on the power calculation of interaction between HER-2 polymorphism and smoking with breast cancer. A large-sample approximation method is used to estimate the power and efficiency of gene-environment interactions. In the basic scenario, power of interaction between HER-2 polymorphism and smoking of unmatched case-control study appears to be 30% while in the frequency matching case-control study it is 56%. However, when increasing the smoking prevalence in controls, greater power can be obtained (power = 74%). CONCLUSIONS: Flexible matching strategies can increase the power and efficiency of case-control studies to detect and estimate the gene-environment interactions when compared with traditional frequency matching and it is especially useful under those scenarios when low environmental exposure of population, adverse gene-environment interactions or less paired controls are seen. Optimal matching design should be made available by weighing the benefits and loss due to flexible matching.

[Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

OBJECTIVE: To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. METHODS: A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. CONCLUSION: The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

[Application of multifactor dimensionality reduction on the interactions between gene-gene, gene-environment and the risk sporadic colorectal cancer in Chinese population].

OBJECTIVE: To identify the association between risk of sporadic colorectal cancer and the common single nucleotide polymorphisms (SNPs) in DNA repairs genes, gene to gene interactions among them and their gene to environment interactions with common environmental factors. METHODS: In this population-based case-control study, 206 primary colorectal cancer cases and 845 cancer-free healthy controls were enrolled. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, with the status of subjects case or controls unknown. Multifactor dimensionality reduction (MDR) and logistic analysis were both used for association analysis. RESULTS: As compared to the younger age group (> or = 42, < 61 years), the risk of colorectal cancer in older age group (> or = 61 years) increased significantly (OR = 2.04, 95% CI: 1.49-2.80). Similar result was observed in the family cancer history (OR = 1.51, 95% CI: 1.05-2.17). However, no significant association between any single DNA repair gene SNP and colorectal cancer risk was discovered. Results from MDR analysis only showed a significant interaction among the four following factors: age, alcohol drinking, XRCC1 Arg194Trp and OGG1 Ser326Cys (the cross-validation consistency = 10/10, the average testing accuracy = 0.616, P = 0.011). Using a logistic regression model, the "high-risk" individuals had a significantly elevated risk of colorectal cancer compared to those "low- risk" individuals classified by the above MDR model (OR = 2.72, 95% CI: 1.66-4.47). CONCLUSION: The impact of polymorphisms in DNA repair genes on the risk of sporadic colorectal cancer exhibited a low-penetrance characteristics while the intricate interactions existing among them and with environmental factors.

[Association of p53 polymorphisms and its haplotypes with susceptibility of breast cancer].

OBJECTIVE: To investigate the association of p53 polymorphisms with susceptibility to breast cancer in Chinese Han population. METHODS: In this population-based case-control study, 84 cases with breast cancers and 168 controls, matched to the cases in terms of gender, habitation and age (5 years), were genotyped for codon 72, intron 3, and intron 6 polymorphisms in p53 gene by polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP) methods. The haplotype distribution was estimated and compared by EH linkage software 1. 2. RESULTS: The distributions of age, alcohol drinking, family history of cancer in first and second relatives were not significantly different between cases and controls. There was significant association between cigarette smoking and breast cancer (chi(2)=6.455, P=0.018), the percentage of ever or current smokers was significantly higher in cases (7.1 %) than that in controls (1.2%). The distributions of allelotype and genotype of codon72, intron 3, and intron 6 were also not significantly different between cases and controls (P>0.05). No significant association was found between the risk of breast cancer and p53 polymorphisms. The genetic linkage disequilibrium existed in these three polymorphic sites in controls, and the Arg-A-G and Pro-A-G were the most common haplotypes both in cases and controls. There was no significant association of p53 haplotype with risk of breast cancer. CONCLUSION: p53 codon72, intron 3, and intron 6 polymorphisms may not be associated with the susceptibility of breast cancer. The Arg-A-G and Pro-A-G haplotypes are the most common haplotypes in Chinese Han population.

[Correlations of single nucleotide polymorphisms of DNA repair gene XRCC1 to risk of colorectal cancer].

BACKGROUND & OBJECTIVE: X-ray repair cross complementing group 1 (XRCC1) encodes a protein required for DNA base excision repair and single strand break recombination repair. The polymorphisms of XRCC1 affect the function of the protein, therefore, affect the susceptibility of human to cancers. This population-based case-control study was to examine the correlations of the 3 most common single nucleotide polymorphisms (SNPs) of XRCC1 gene, C26304T, G27466A and G28152A, to risk of colorectal cancer. METHODS: XRCC1 genotypes in 207 colorectal cancer patients and 621 matched healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP). The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model to evaluate the correlations of the 3 genotypes to risk of colorectal cancer. The haplotype distribution was estimated by EH linkage software 1.2. RESULTS: There was no significant differences in selected characteristics, such as age, sex, body mass index, cigarette-smoking and alcohol-drinking status, between the patients and the controls. The frequencies of mutant 26304T, 27466A, and 28152A alleles were 29.95%, 11.22%, and 28.22%, respectively, in the patients, and 32.87%, 12.34%, and 27.27%, respectively, in the controls; there was also no significant difference between the 2 groups. All the polymorphic genotypes met the Hardy-Weinberg equilibrium. No significant correlation of XRCC1 C26304T, G27466A, and G28152A polymorphisms to risk of colorectal cancer was found. Estimated by EH linkage software 1.2, genetic linkage disequilibrium existed both in the patients and the controls, and CGG, CGA, CAG, and TGG were the 4 most common haplotypes. However, there was no significant difference in haplotype distribution between the 2 groups (95.54% vs. 96.64%, P>0.05). CONCLUSIONS: In Han people in southern China, XRCC1 C26304T, G27466A, and G28152A polymorphisms have no correlations to risk of colorectal cancer. However, the genetic linkage disequilibrium exists in these 3 polymorphic sites, and CGG, CGA, CAG, and TGG are the 4 most common haplotypes.

[Association between genetic polymorphisms in folate metabolic enzyme genes and colorectal cancer: a nested case-control study].

OBJECTIVE: To investigate the interrelationship of genetic polymorphisms in folate metabolic enzymes (MTHFRC677T, MTHFRA1298C, MTRA2756G and MTRRA66G) and their combinative effects with colorectal cancer (CRC). METHODS: A nested case-control study was designed and carried out. 140 CRC patients and 343 control subjects were included in this study. Polymorphisms of folate metabolic enzyme genes were genotyped by PCR-restriction fragment length polymorphism method. Risk of CRC was estimated by unconditional logistic model, and P value for interaction was calculated by likelihood test. RESULTS: The allele of MTR2756G showed a positive association with CRC (OR = 2.04, 95% CI = 1.22 - 3.40). Those with MTHFR1298AA and MTR 2756AG/GG genotypes had an elevated risk with CRC (OR = 2.57, 95% CI, 1.42 -4.65), and their combinative effect showed a significant association with CRC (P = 0.04). CONCLUSION: MTR2756G allele may be a risk factor of CRC, and interaction may exsit between polymorphisms of MTHFRA1298C and MTRA2756G. Further studies with larger sample and in different ethnic groups are needed.