GG genotype of cyclin D1 G870A polymorphism is associated with non-cardiac gastric cancer in a high-risk region of China

Objective. Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle of both normal and neoplastic cells. Polymorphism of this gene at codon 242 in exon 4 (A870G) has an impact on the risk of several human cancers. The purpose of this study was to study the relation between the CCND1 A870G gene polymorphism and the risk of non-cardiac gastric cancer in a Chinese population. Material and methods. The study population consisted of 159 patients with non-cardiac gastric cancer and 162 cancer-free controls. CCND1 870A/G polymorphism was genotyped by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and sequencing. Results. CCND1 genotype distribution among the patients was significantly different from that among controls; AA (odds ratio (OR)=0.348, 95% CI: 0.163–0.742) and GA (OR=0.715, 95% CI: 0.506–1.012) genotypes were significantly lower in the gastric cancer patients than in the controls when subjects with the GG genotype served as the reference category. In other words, the risk of gastric cancer for subjects with the GG genotype was 2.8 times that of subjects with the AA genotype, and 1.4 times that of subjects with the GA genotype. Furthermore, in the stratification analyses, the risk of GG genotype was more evident in subjects ≥60 years of age and those positive for Helicobacter pylori (H. pylori) infection. Conclusions. The CCND1870 GG genotype is associated with an increased risk for non-cardiac gastric cancer in patients in a high-risk area of China. Larger studies with multiple polymorphisms are needed to verify this finding and the function of this polymorphism needs to be further investigated.     

Prognostic importance of DNA repair gene polymorphisms of <Emphasis Type="Italic">XRCC1</Emphasis> Arg399Gln and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln in lung cancer patients from India

Purpose Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive. Methods In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population. Logistic regression models were fit to examine the relationship between the log odds of lung cancer and each covariate. Overall Survival in relation to various genotypes and clinicopathological factors were analyzed using Kaplan Meier estimates and hazard ratios were calculated using Cox Regression analysis. Results The carriers of XRCC1 399 AA genotypes were at higher risk of lung cancer (OR = 2.1, 95% CI:1.224–3.669, P = 0.007) than carriers of GG genotype. Subjects carrying 751 AC genotype were at an increased risk of carcinoma of the lung (OR = 1.8; 95% CI:1.233–2.807, P = 0.003) than subjects with AA genotypes. Compared to the XRCC1 399 GG/ XPD 751 AA reference genotype, the combined variants, XRCC1 399 GG/ XPD 751 AC+CC (OR = 1.9, 95% CI: 1.037–3.481), P = 0.03), XRCC1 399 GA+AA/ XPD 751 AA (OR = 1.7, 95% CI: 1.020–2.833, P = 0.04), XRCC1 399 GA+AA/XPD 751 AC+CC (OR = 2.7, 95% CI: 1.582–4.864, P = 0.01), had significantly higher odds ratios. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival, the risk being significant for the XRCC1 gene polymorphism (P = 0.01 by log-rank test). The hazard of dying was significant for the XRCC1 399 AA genotype (HR = 3.04, 95%CI: 1.393–6.670, P = 0.005). Higher tumour stage also came out as significant predictors of patient death. Conclusions These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.     

Two single nucleotide polymorphisms in ALOX15 are associated with risk of coronary artery disease in a Chinese Han population

Arachidonate 12/15-lipoxygenase (12/15-LOX) has been implicated in the pathogenesis of atherosclerosis, but with contradicting results. The aim of this study was to investigate the association of two polymorphisms in ALOX15 and the risk of coronary artery disease (CAD) in a Chinese Han population. A total of 519 unrelated CAD patients and 608 unrelated control subjects of the Chinese Han population were recruited in the case-control study. Two tagSNPs, rs7217186:T>C and rs2619112:G>A, were selected and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The carriers of the C allele (the CC homozygote and the CT heterozygote) of rs7217186:T>C and the carriers of the A allele (the AA homozygote and the GA heterozygote) of rs2619112:G>A displayed elevated odds ratios (ORs) for CAD compared with the TT homozygotes and GG homozygotes, respectively, after adjusting for other potential confounders including age, sex, body mass index, systolic blood pressure, diastolic blood pressure, glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and smoking status (adjusted odds ratio [OR] = 3.2, 95% confidence interval [CI]: 1.335–7.665, P = 0.009 and adjusted OR = 3.5, 95% CI: 1.343–9.330, P = 0.011). In stratified analyses, after adjusting those aforementioned confounders, the CC and CT genotypes of rs7217186:T>C were associated with a greater risk of CAD in subjects <60 years (adjusted OR = 5.7, 95% CI: 1.557–21.097, P = 0.009) and in females (adjusted OR = 9.3, 95% CI: 1.048–82.213, P = 0.045). For rs2619112:G>A, subjects (<60 years) carrying the A allele had a greater risk of CAD than the GG homozygotes (adjusted OR = 4.9, 95% CI: 1.215–19.547, P = 0.025); the male carriers of A allele also had a greater risk (adjusted OR = 3.5, 95% CI: 1.136–11.006, P = 0.029). In summary, the present study shows that after adjustment for other confounding CAD factors, rs7217186:T>C and rs2619112:G>A of ALOX15 are associated with increased risk of CAD in this Chinese Han population.     

CYP1B1 Asn453Ser polymorphism and colorectal cancer risk: a meta-analysis

Studies investigating the association between cytochrome P450 1B1 (CYP1B1) Asn453Ser (453 A/G, rs1800440) polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline and Embase Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP1B1 polymorphism and CRC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. The pooled ORs were performed for co-dominant model (GG vs AA, GA vs AA), dominant model (GG+GA vs AA), and recessive model (GG vs GA+AA). This meta-analysis included 7 case-control studies, which included 6375 CRC cases and 7003 controls. Overall, the variant genotypes (GG and GA) of the 453 A/G were not associated with CRC risk when compared with the wild-type AA homozygote (GG vs AA, OR=0.94, 95% CI=0.77-1.14; GA vs AA, OR=0.99, 95% CI=0.87-1.12). Similarly, no associations were found in the dominant and recessive models (dominant model, OR=0.98, 95% CI=0.87-1.09; recessive model, OR=0.94, 95% CI=0.77-1.14). When stratifying for country, study sample size, matched control and source of controls, no evidence of significant association was observed in any subgroup, except among those studies from "Canada". No publication bias was found in the present study. No association was found between the CYP1B1 Asn453Ser polymorphism and risk of CRC among Caucasians.     

Lack of association between TNF 238 G/A polymorphism and type 2 diabetes: a meta-analysis

The aim of this meta-analysis was to determine the nature of the association between TNF 238 G/A polymorphism and the risk for T2D. We searched databases updated on January 2009 for all publications on the association between this variation and T2D. Data on genotypes and the numbers of cases and controls were assessed using Review Manager 4.2. Meta-analysis of the overall and specific populations was conducted, and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the fixed-effect model. I ² statistic was calculated to examine heterogeneity, and publication bias was evaluated by Egger test. The overall OR (95% CI) for AA and GA genotypes versus GG genotype for TNF-α-238 was 1.15 (0.92–1.44), which in European and Asian populations were 1.18 (0.92–1.51) and 1.13 (0.62–2.04), respectively. This first meta-analysis of data from the current and published studies did not detect any association between the polymorphism of TNF 238 G/A and risk for T2D.     

Polymorphisms of drug‐metabolizing genes and risk of non‐Hodgkin lymphoma

Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug‐metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non‐Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population‐based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)_AG = 0.67, 95% confidence interval (CI) = 0.55–0.82; OR_AG/GG = 0.66, 95% CI = 0.54–0.80) and DLBCL (OR_AG = 0.63, 95% CI = 0.49–0.82; OR_AG/GG = 0.64, 95% CI = 0.50–0.82). For T‐cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (OR_AG/GG = 0.65, 95% CI = 0.44–0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (OR_AG = 1.28, 95% CI = 1.07–1.54; OR_AG/GG = 1.26, 95% CI = 1.06–1.51) and DLBCL (OR_AG = 1.32, 95% CI = 1.04–1.66; OR_AG/GG = 1.30, 95% CI = 1.03–1.63), but not T‐cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis—results and the review of the literature

Autoimmune thyroid diseases frequently overlaps with rheumatoid arthritis (RA). Among genetic factors, the role of the HLA antigens and CTLA4 gene polymorphisms in the overlapping has been suggested. The aim of this study was to investigate the alleles and genotypes frequency of the CTLA4 exon1 A49G polymorphism in Slovak patients with RA, Hashimoto thyroiditis (HT), both (RA + HT) and in healthy controls. Fifty-seven unrelated adults with RA, 57 patients with HT, 34 patients with both (RA + HT), and 51 normal subjects were studied. All were ethnic Slovaks living in the same geographical area. The CTLA4 exon1 A49G polymorphism was genotyped by using small amplicon melting analysis after real-time PCR. The CTLA4 49GG genotype and G allele frequency in the group with RA was not significantly higher in comparison with controls (10.53% vs. 9.8%, p = 0.62, OR 1.39, 95% CI 0.35–5.74 and 39.47% vs. 34.31%, p = 0.43, OR 1.25, 95% CI 0.72–2.18). The frequency of GG genotype was slightly but not significantly higher in patients with HT as compared with control group (19.3% vs. 9.8%, p = 0.17, OR 2.27, 95% CI 0.67–8.45). However, the frequency of GG genotype and G allele in patients with both RA and HT was significantly higher than that in controls (29.41% vs. 9.8%, p = 0.02, OR 4.49, 95% CI 1.20–18.54 and 51.47% vs. 34.31%, p = 0.03, OR 2.02, 95% CI 1.08–3.81). The frequency of GG genotype of CTLA4 A49G gene polymorphism in Slovak patients with RA is not significantly higher in comparison to control group. However, carriers of GG genotype with RA may be susceptible to develop HT.     

MALAT1 rs619586 A/G polymorphisms are associated with decreased risk of lung cancer

Lung cancer is the leading cause of cancer-associated mortality worldwide. Genetic factors are reported to play important roles in lung carcinogenesis. To evaluate genetic susceptibility, we conducted a hospital-based case-control study on the effects of functional single nucleotide polymorphisms (SNPs) in long non-coding RNAs (lncRNAs) and microRNAs on lung cancer development. A total of 917 lung cancer cases and 925 control subjects were recruited. The MALAT1 rs619586 A/G genotype frequencies between patient and control groups were significantly different (P < .001), specifically, 83.85% vs 75.88% (AA), 15.60% vs 21.79% (AG), and 0.55% vs 2.32% (GG). When the homozygous genotype MALAT1 rs619586 AA was used as the reference group, AG (AG vs AA: adjusted odds ratio [OR] 0.65, 95% confidential interval [CI] 0.51–0.83, P = .001) and GG genotypes were associated with significantly decreased risk of lung cancer (GG vs AA: adjusted OR 0.22, 95% CI 0.08–0.59, P = .003). In the dominant model, MALAT1 rs619586 AG/GG variants were also associated with a significantly decreased risk of lung cancer (adjusted OR 0.61, 95% CI 0.48–0.78, P < .001). In the recessive model, when MALAT1 rs619586 AA/AG genotypes were used as the reference group, the GG homozygous genotype was also associated with significantly decreased risk for lung cancer (adjusted OR 0.24, 95% CI 0.09–0.64, P = .004). Hsa-miR-34b/c rs4938723 T > C, pri-miR-124-1 rs531564 C > G and hsa-miR-423 rs6505162 C > A SNPs were not associated with lung cancer risk. Our collective data indicated that MALAT1 rs619586 A/G SNPs significantly reduced the risk of lung cancer. Large-scale studies on different ethnic populations and tissue-specific biological characterization are required to validate the current findings.     

The predictive value of CTLA-4 and Tg polymorphisms in the recurrence of Graves' disease after antithyroid withdrawal

Graves’ disease (GD) is a multifactorial disease that develops as a result of complex interactions between genetic and environmental factors. The aim of our study is to determine the frequency of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) A/G and TG C/T exon 33 SNPs (Tg E33SNP) in GD and to evaluate the relation between recurrence and these polymorphisms. A total of 187 subjects, including 97 previously treated GD patients and 90 age and gender matched control subjects were studied. We examined the relationship between the A/G and C/T polymorphism and various clinical and laboratory variables among patients with GD. TT genotype frequency in the GD patients was significantly higher than the controls. Number of recurrent patients was significantly higher in AG and GG carriers in comparison to AA carriers (57% and 45% vs 14%, p=0.0001). CTLA-4 AG genotype had an eightfold (OR:8.050;95% CI:2.87−22.5; p=0.0001) and GG genotype had a sevenfold (OR: 7.025; 95% CI: 1.67−29.4; p=0.007) increase in the risk of recurrence in the patients with GD. In conclusion, early interpretation for definitive treatment procedures (i.e., radioactive iodine or surgery) may be considered in the patients with G allele and E33SNP of Tg gene is conformed the susceptibility to GD in a Turkish population and having TT genotype increases the susceptibility to GD.     

Effects of Interleukin-10 -1082G/A and -592C/A Gene Polymorphisms on the Risk of Human Immunodeficiency Virus-1 Infection: An Updated Meta-analysis

This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The correlation was not significant between -1082G/A polymorphism and HIV-1 susceptibility (allelic model (G vs. A: OR (95% CI)=0.968 (0.878-1.067)); recessive model (GG vs. AA+AG: OR (95% CI)=0.940, (0.771-1.146)); dominant model (GG+AG vs. AA: OR (95% CI)=0.967(0.846-1.106)); homozygous model (GG vs. AA: OR (95% CI)=0.971(0.780-1.209)); heterozygous model (AG vs. AA: OR (95% CI)=0.988(0.797-1.224)) and over-dominant model (GG+AA vs. AG: OR (95% CI)=0.969(0.781-1.201)). IL-10-592C/A polymorphism might be related to HIV-1 in allelic model, dominant model, homozygous model and heterozygous model (OR (95% CI)(0.796-0.965); OR (95% CI)=0.793(0.664-0.948); OR (95% CI)=0.755,(0.612-0.930); OR (95% CI)=0.820(0.679-0.991), respectively), but not to recessive model and over-dominant model (OR (95% CI)=0.882(0.770-1.010) and OR (95% CI)=1.009(0.897-1.148)).     

COX-2 polymorphisms -765G →C and -1195A→G and colorectal cancer risk

AIM： TO determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer （CRC） in a Dutch population. METHODS： This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -7dEG→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS： The -765GG genotype was associated with an increased risk of developing CRC （OR, 1.45; 95% CI, 1.03-2.04）. No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls （OR 0.44; 95% CI, 0.22-0.85）. When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls （OR（AG/AC） 0.78; 95% CI, 0.57-1.06）. CONCLUSION： The -765GG genotype is associated with an increased risk of developing CRC and the G6/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.     

Vitamin D and estrogen receptor gene polymorphisms and the risk of colorectal cancer in Bulgaria

Background and aims Different epidemiological studies report the protective effect on colorectal cancer (CRC) exerted by vitamin D₃ intake, estrogen replacement therapy, and increase of the risk of microsatellite instability (MSI) in CRC by withdrawal of estrogens. The aim of our study was to search for association between CRC and polymorphisms in estrogen receptor-α (ER-α) and Vitamin D receptor (VDR) genes. Materials and methods We analyzed the PvuII and XbaI polymorphisms from the ER-α gene and the BsmI polymorphism of the VDR gene in 140 patients with CRC (subsequently divided according to their MSI status) and 94 controls. Results We have demonstrated that the presence of the PvuII pp genotype increased the risk of developing MSI(+) tumors about three times compared to MSI(−) tumors [odds ratio (OR)=3.09, 95% confidence interval (CI) 0.88–10.91]. The effect of the XbaI xx genotype was similar (OR=2.08, 95% CI 0.49–8.81). Our results for the VDR BsmI polymorphism showed an increased risk for CRC in bb carriers (OR=1.8, 95% CI 0.81–4.05). Conclusion We conclude that PvuII and XbaI polymorphisms in the ER-α gene were associated with the risk of developing MSI in CRC patients. The BsmI polymorphism in the VDR gene was linked to the risk of developing CRC.     

环氧化酶-2基因启动子区多态性与结直肠癌的易感性

目的:探讨环氧化酶-2(cyclooxygenase-2,COX-2)基因启动子区的-1195(G/A,rs689466)及3’非翻译区的8473(T/C,rs5275)2个位点的基因多态性与结直肠癌(colorectal cancer,CRC)发病风险的相关性.方法:采用病例-对照研究,利用聚合酶链式反应和限制性片段长度多态性(polymerase chain reaction-restrictive fragment length polymorphism,PCR-RFLP)分析方法,对343例CRC患者和340例健康人的COX-2基因的2个位点的多态性进行检测,采用SPSS11.0软件包统计分析各位点的基因型分布和等位基因频率.结果:COX-2-8473位点多态性的各基因型频率在病例组及对照组中分布均无显著差异(P>0.05),但COX-2-1195位点多态性的基因型频率在二组中分布有显著性差异(P<0.001),结果显示CRC患者COX-2-1195AG基因型在病例组的频率较对照组显著增高(校正后OR=2.23;95%CI:1.50-3.32),AA基因型在病例组中的频率亦较对照组高(校正后OR=2.46;95%CI:1.51-4.02),A等位基因携带者在病例组中的频率高于对照组(校正后OR=2.27;95%CI:1.55-3.34).各基因型分布在结肠癌及直肠癌中的分布无显著性差异(P>0.05).COX-2-1195A等位基因与淋巴结转移及TNM分期有显著相关性.结论:COX-2-1195位点AG/AA基因型是CRC的风险因素,且与CRC的淋巴结转移及TNM分期相关.     

Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China

Abstract

Purpose: This study investigated correlations between polymorphisms in DNA mismatch repair (MMR) genes and the risk of primary hepatocellular carcinoma (PHC). Methods. Single nucleotide polymorphisms (SNPs) in the DNA MMR genes MLH3 (rs175080), PMS1 (rs5742933), PMS2 (rs1059060), MSH3 (rs26279), MSH5 (rs1150793, rs2075789) and MSH6 (rs1042821) were detected using the SNaPshot method in 250 PHC cases and in 308 patients without PHC in the Han population in northern China. Results. The AA genotype in MLH3 (rs175080) increased the risk of PHC (odds ratio [OR] = 3.424; 95% confidence interval [CI]: 1.097–10.689). The AG and GG genotypes in MSH3 (rs26279) increased the risk of PHC (OR: 1.644 and 3.300; 95% CI: 1.112–2.428 and 1.765–6.168, respectively). The AA genotype in MSH5 (rs2075789) increased the risk of PHC (OR: 9.229; 95% CI: 1.174–72.535). The CT genotype in MSH6 (rs1042821) reduced the risk of PHC (OR: 0.629; 95% CI: 0.428–0.924). Conclusions. Our study suggests that polymorphisms in MLH3 (rs175080), MSH3 (rs26279), MSH5 (rs2075789) and MSH6 (rs1042821) may be independent risk factors for PHC.     

Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis

We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) and AA?+?AG vs. GG (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR?=?1.383, 95 % CI 1.142–1.676, P?=?0.022) and AA vs. AG?+?GG (OR?=?1.575, 95 % CI 1.361–1.823, P?<?0.001) in European patients with Crohn’s disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG?+?GG (OR?=?0.713, 95 % CI 0.545–0.933, P?=?0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD.     

Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in Turkish patients

Rheumatoid arthritis (RA) is an autoinflammatory disease with a genetic background. The synoviocytes in RA shows cellular transformation with tumor-like features, and RA patients have genomic instability and relaxation of DNA repair mechanisms. The polymorphisms in BER repair pathway genes, XRCC1 and OGG1, may change the response to inflammation via altered DNA repair capacity. In this study, we aimed to investigate the relationship between the risk of RA and XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms in a group of Turkish RA patients. XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms were investigated by PCR–RFLP method in 100 RA patients and 158 healthy control subjects. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ²-tests. RA patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism in both homozygote (GG) (35%, OR: 7.78 [95% CI: 3.65–16.59], P < 0.001) and heterozygote (AG) forms (41%, OR: 2.17 [95% CI: 1.19–3.96], P < 0.01) and also increased frequency of 399Gln (G) allele (55%, OR:2.99 [95% CI: 1.67–5.37], P < 0.001). We conclude that XRCC1 Arg194Trp, and OGG1 Ser326Cys polymorphisms are not associated with RA; however, Arg399Gln polymorphism is a significant risk factor of RA, and carriers of 399Gln (G) allele have greater risk of RA.     

Genetic polymorphisms in IL10RA and TNF modify the association between blood transfusion and risk of non-Hodgkin lymphoma

We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes may modify the association between blood transfusion and risk of non-Hodgkin lymphoma (NHL). Compared with women without blood transfusion, women with a history of transfusion had an increased risk of NHL if they carried IL10RA (rs9610) GG genotype [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.1-3.2] or TNF (rs1800629) AG/AA genotypes (OR = 1.6, 95% CI: 0.9-2.7). We also found women with a history of transfusion had a decreased risk of NHL if they carried IL10RA (rs9610) AG/AA genotypes (OR = 0.6, 95% CI: 0.4-0.9) or TNF (rs1800629) GG genotype (OR = 0.7, 95% CI: 0.5-1.0). A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. Statistically significant interactions with blood transfusion were observed for IL10RA (rs9610) (P(forinteraction) = 0.003) and TNF (rs1800629) (P(forinteraction) = 0.012) for NHL overall and IL10RA (rs9610) (P(forinteraction) = 0.001) and TNF (rs1800629) (P(forinteraction) = 0.019) for B-cell lymphoma. The results suggest that genetic polymorphisms in TNF and IL10RA genes may modify the association between blood transfusion and NHL risk.     

Impact of pepsinogen C polymorphism on individual susceptibility to gastric cancer and its precancerous conditions in a Northeast Chinese population

Purpose  Human pepsinogen C (PGC) is an aspartic protease produced specifically by the gastric mucosa, and is considered as a mature marker of gastric epithelium. This study examined the contributions of PGC polymorphisms and the Helicobacter pylori (H. pylori) infection to the risk of gastric cancer (GC), and its precancerous conditions in a Northeast Chinese population. Methods  The PGC insertion/deletion polymorphism was evaluated by polymerase chain reaction analysis, followed by direct DNA sequencing in 564 cases of GC, atrophic gastritis (AG), gastric ulcer (GU) and superficial gastritis (as control). All cases were frequency-matched 1:1 by gender and age (±5). H. pylori infection was identified by serum anti-H. pylori IgG measurement through enzyme-linked immunosorbent assay. Results  Patients with a homozygous PGC allele 1 genotype had a significant risk of AG [adjusted odds ratio (OR) 3.11; 95% confidence interval (CI) 1.44–6.71] or of GC (OR 3.00; 95% CI 1.38–6.51), and a significantly elevated risk of intestinal metaplasia (OR 1.90, 95% CI 1.11–3.27). PGC polymorphism with H. pylori infection increased risk of GU (OR 8.69; 95% CI 1.01–74.69), and AG (OR 11.12; 95% CI 1.37–90.84) or GC (OR 10.61; 95% CI 1.28–87.79) in a super-multiplicative manner. The S value was 5.40, 6.48 and 4.34; and the AP value was 72.09, 7.00 and 69.69%, respectively. Conclusions  The PGC gene polymorphism increases an individual’s susceptibility to GC and its precancerous conditions. Moreover, the PGC gene polymorphism shows a positive link to H. pylori infection in the development of GC.     

细胞周期素D1基因多态性与胃癌关系的研究

目的 研究与肿瘤发生有关的细胞周期蛋白D1(CCND1)870A/G基因多态性与胃癌易感性的关系.方法 收集106例胃癌病例(包括胃体癌及胃窦癌)和108例非溃疡性消化不良患者的外周血白细胞,采用病例对照分子流行病学研究方法 ,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,进行CCND1基因型检测.结果 在病例组和对照组中CCND1 870位点野生型GG频率分别为19.8%和7.4%,携带AA基因型个体发生胃癌危险是携带GG型个体的0.28倍(P＜0.05,OR=0.281),即GG型个体更易感胃癌.分层分析表明,携带GG基因型个体分别在男性、年龄≥60岁及幽门螺杆菌感染亚组中患胃癌风险更高.结论 在中国胃癌高发区西安,CCND1 870A/G位点GG基因型人群更易感胃癌.