Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study

Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1β and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1β -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11–0.62; p = 0.002; OR = 0.462; 95% CI = 0.253–0.845, p = 0.01). In conclusion, subjects with IL-1β -511TT genotype or IL-1β*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.     

中国北方地区汉族人群MCP-1基因多态性与肺癌相关性研究

目的 探讨中国北方地区汉族人群单核细胞趋化因子蛋白-1(monocyte chemoattrac-tant protein 1,MCP-1)基因-2518位点多态性与肺癌的相关性.方法 应用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)的方法对中国北方地区汉族人群134例肺癌患者和82例正常对照进行MCP-1基因-2518位点基因多态性检测.结果 AA基因型和GG基因型频率在肺癌病人和对照组间差异有统计学意义.AA基因型患肺癌的相对风险度增加(OR=2.645,X~2=6.532,P=0.011),GG基因型患肺癌的相对风险度降低(OR=0.519,X~2=4.929,P=0.026).肺癌病人中非小细胞肺癌患者AA基因型和GG基因型频率在病人和对照组间差异有统计学意义,AA基因型患病的相对风险度增加(OR=3.138,X~2=8.905,P=0.003),GG基因型患病的相对风险度降低(OR=0.516,X~2=4.613,P=0.032).小细胞肺癌患者各基因型频率与对照组差异无统计学意义.结论 中国北方地区汉族人群MCP-1基因-2518位点多态性与非小细胞肺癌相关,与小细胞肺癌不相关.     

Lack of association between DNA repair gene ERCC1 polymorphism and risk of lung cancer in a Chinese population

The ERCC1 (Excision Repair Cross Complementation Group 1) gene is involved in the nucleotide excision repair pathway. This study was designed to examine whether ERCC1 Asn118Asn (G19007A) polymorphism, which has been associated with risk of some cancers among Caucasians, may be associated with risk of lung cancer in a Chinese population. ERCC1 Asn118Asn (G19007A) genotypes were determined in DNA samples from 151 cases and 143 controls. The distribution of genotypes between cases and controls was not associated with an increased risk of lung cancer (AA versus GG: adjusted OR (odds ratio) = 1.41, 95% CI (confidence interval) = 0.76-2.59; AG versus GG: adjusted OR = 0.78, 95% CI = 0.47-1.29; and AA + AG versus GG: adjusted OR = 0.93, 95% CI = 0.73-1.19). The frequency A (0.20) of the A-allele was significantly lower among these Chinese controls than in the Caucasian control populations (A = 0.54-0.65) (All P < 0.001). No statistically significant effects of age, histological subtype or smoking were found. These findings suggest that ERCC1 Asn118Asn (G19007A) polymorphism may play a limited role for lung cancer in this Chinese population.     

The association between mannose-binding lectin gene polymorphism and rheumatic heart disease

Mannan-binding lectin (MBL) is an innate pattern recognition molecule known to play a key role in pathogen clearance. As MBL2 gene polymorphism is associated to an increased susceptibility to infection, we aimed to determine genetic variations in the MBL2 gene in rheumatic heart disease (RHD). Genetic variations in the promoter and exon 1 region of the MBL2 gene were analyzed in 107 patients with RHD and 105 controls by real-time polymerase chain reaction. The frequency of MBL2* A/A genotype was significantly higher in RHD patients (71/107, 66.36% vs 52/105, 49.52%, p ≤ 0.02, OR = 1.99, 95% CI, 1.15–3.50). A/A genotypes were associated with higher levels of MBL in RHD compared with controls with the same genotype (p ≤ 0.004). The frequency of HYPA/HYPA, HYPA/LYQA, and LYQA/LYQA haplotypes was also increased in RHD (p ≤ 0.03, OR = 1.98, 95% CI, 1.05–3.73). However, the frequency of MBL2 variant alleles (termed “O”) was lower among patients (39/214, 18.2% vs 63/210, 30.0%, p ≤ 0.006, OR = 0.52, 95% CI, 0.33–0.82), which was also seen for O/O genotypes (3/107, 2.8% vs 10/105, 9.5%, p ≤ 0.05, OR = 0.27, 95% CI, 0.07–1.03). This data suggests a role for MBL genotypes in the susceptibility to RHD. However, it still remains unclear whether A/A homozygosity is a risk factor for RHD or rheumatic fever itself.     

Caspase 9 promoter polymorphisms and risk of primary lung cancer

Caspase-9 (CASP-9) is an initiator CASP in the apoptosome-driven apoptosis pathway and plays an important role in the development and progression of cancer. Polymorphisms in the promoter region of the CASP-9 gene may influence the promoter activity of this gene, thereby modulating susceptibility to lung cancer. To test this hypothesis, we examined the association of four polymorphisms [-1263A>G, -905T>G, -712C>T and -293_-275delCGTGAGGTCAGTGCGGGGA (-293del)] in the CASP-9 promoter with the risk of lung cancer in a Korean population. The CASP-9 genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and gender. The -1263 GG genotype was associated with a significantly decreased risk of lung cancer compared with the -1263 AA genotype or combined -1263 AA+AG genotype [adjusted odds ratio (OR)=0.64, 95% confidence interval (95% CI)=0.42-0.98, P=0.04 and adjusted OR=0.67, 95% CI=0.46-0.97, P=0.01, respectively]. For the -712C>T polymorphism, individuals with at least one -712T allele were at a significantly increased risk of lung cancer compared with those harboring the -712 CC genotype (adjusted OR=1.42, 95% CI=1.06-1.89, P=0.02). Consistent with the results of genotype analyses, the -1263G/-712C (G-C) haplotype was associated with a significantly decreased risk of lung cancer [adjusted OR=0.59, 95% CI=0.47-0.75, P and Bonferroni corrected P (Pc)<0.001]. Moreover, the risk of lung cancer decreased in a dose-dependent manner as the number of the G-C haplotypes increased (adjusted OR=0.60, 95% CI=0.45-0.81, P=0.0007 and Pc=0.0014 for the G-C heterozygotes and adjusted OR=0.34, 95% CI=0.17-0.68, P=0.0023 and Pc=0.0046 for the G-C homozygotes; P(trend)<0.001). The promoter assay revealed the G-C haplotype to have a significantly higher promoter activity than the -1263G/-712T and -1263A/-712C haplotypes. These results suggest that CASP-9 promoter polymorphisms affect CASP-9 expression and contribute to genetic susceptibility to lung cancer.     

Common germline MDR1/ABCB1 functional polymorphisms and haplotypes modify susceptibility to colorectal cancers with high microsatellite instability

Altered expression of P-glycoprotein (P-gp) encoded by the multidrug resistance (MDR1/ABCB1) gene, as well as somatic mutations and hypermethylation in the MDR1/ABCB1 gene, were identified in a proportion of previously untreated colorectal cancers (CRC) exhibiting high microsatellite instability (MSI-H), which suggested that MDR1/ABCB1 acts as a candidate gene contributing to the initiation and progression of MSI-H tumors. Here we report germline functional single nucleotide polymorphisms (SNPs) and haplotypes in the MDR1/ABCB1 gene, which could contribute to genetic risk or increase susceptibility to MSI-H cancers. We have confirmed disease association by comparing the MDR1/ABCB1 genotype, allele, and haplotype frequencies between healthy controls and patients with MSI-H tumors. In particular, carriers of the T/T genotype in exon 12 (1236 C→T) SNP and the T/T genotype in exon 21 (2677G→T) SNP were most significantly associated with a higher risk for developing MSI-H CRC compared to controls (P=0.01, OR=3.182 and P=0.005, OR=3.594, respectively). The most significant MSI-H–associated risk haplotypes include the most frequent haplotype H1 (T-C-T-T) defined by SNPs in exon 12, intron 13 (rs2235035), exon 21, and exon 26 (3435 C→T; P=0.004, OR= 0.476). Our results suggest that ABCB1/MDR1 is a novel low-penetrance gene for susceptibility to MSI-H tumors. The present study provides additional evidence for the role that the MDR1/ABCB1 gene plays in the initiation and progression of MSI-H CRC development. ©2008 Elsevier Inc. All rights reserved.     

PD-1基因遗传变异与上皮性卵巢癌发病风险的关联

目的探讨细胞程序性死亡受体-1(PD-1)基因遗传变异与上皮性卵巢癌发病风险的关系。方法用聚合酶连接酶检测反应技术(PCR-LDR)检测分析620例上皮性卵巢癌患者和620名对照妇女PD-1.1 A/G和PD-1.5 C/T两个单核苷酸多态位点的基因型和等位基因频率。结果 PD-1.1 A/G多态的AA、AG、GG 3种基因型频率在病例组和对照组中具有显著差异(P0.05)。比较AA基因型携带者,AG和GG基因型携带者显著降低上皮性卵巢癌的发病风险(OR=0.71,95%CI=0.54~0.94和OR=0.68,95%CI=0.50~0.94)。病例组中G等位基因频率明显低于对照组(P0.05)。与A等位基因相比,G等位基因显著降低妇女上皮性卵巢癌的发病风险(OR=0.83,95%CI=0.71~0.97)。PD-1.5 C/T多态C和T等位基因频率在2组间具有统计学意义,病例组中T等位基因频率明显低于对照组(P0.05)。与C等位基因相比,T等位基因显著降低妇女上皮性卵巢癌的发病风险(OR=0.82,95%CI=0.69~0.98)。结论 PD-1.1 A/G和PD-1.5 C/T两个单核苷酸多态位点可能是中国北方妇女上皮性卵巢癌发病风险的分子标志物。     

Effect of epoxide hydrolase polymorphisms on chromosome aberrations and risk for lung cancer

Microsomal epoxide hydrolase (mEH) gene is polymorphic and its enzyme is involved in the activation and subsequent detoxification of several tobacco carcinogens, for example polycyclic aromatic hydrocarbons. Therefore, we have investigated the association of two polymorphisms at exons 3 and 4 of the mEH gene with the development of lung cancer in 110 patients and 119 matched controls. In addition, we have investigated the relationship between the different mEH alleles and the frequency of chromosome aberrations (CA), as an approach to understand the role of genetic susceptibility on cancer risk. Our results show that only the homozygous exon 4 fast genotype is significantly associated with increased risk for lung cancer (odds ratio [OR]=6.26; 95% confidence interval [CI]=1.02-38.3). When the exons 3 and 4 polymorphisms are considered together, patients carrying the high enzyme activity genotype have a significantly increased risk for lung cancer (OR=2.46; 95% CI=1.06-5.68). More importantly, the increased risk for this group is confirmed by their having the highest frequency of CA compared to any other genotype groups. In addition, genotypes with higher risk had consistently more CA than those with lower risk. Our CA data also indicates that the low activity genotype may exert a protective role in cigarette smokers, as it was associated with a significant decrease in CA compared to the high and intermediate activity genotypes. In conclusion, the CA data provides evidence to support that susceptibility mEH alleles are significantly involved with the development of lung cancer from cigarette smoking.     

中国苏州地区汉族人群MCP-1基因多态性与急性胰腺炎相关性研究

目的探讨中国苏州地区汉族人群单核细胞趋化因子蛋白-1(monocyte chemoattractant protein-1,MCP-1)基因-2518A/G多态性与急性胰腺炎的相关性。方法采用聚合酶链反应-限制性片段长度多态性方法检测中国苏州汉族人群急性胰腺炎(acute pancreatitis,AP)患者101例[其中包括轻症急性胰腺炎(mildAP,MAP)78例,重症急性胰腺炎(servere AP,SAP)23例]和120名健康对照的MCP-1基因-2518位点基因型分布及基因频率,并评价基因多态性与AP易感性之间的相关性。结果对照组MCP-1-2518A/G位点的AA基因型频率较SAP组和MAP组高,差异有统计学意义(P<0.01),携AG及GG基因型者患MAP的风险度约是AA基因型的5.896倍(P<0.01,OR=5.896),患SAP的风险度约为7.011倍(P<0.05,OR=7.011)。而在MAP与SAP组间AA基因型频率差异无统计学意义(P=0.997)。对照组G等位基因频率明显低于MAP(P<0.01,OR=0.318)和SAP组(P<0.01,OR=0.309)。但G等位基因频率在MAP与SAP组间基因型分布差异无统计学意义(P=0.623,OR=1.211)。结论中国苏州地区汉族人群MCP-1-2518位点AA基因型可能有助于保护机体避免发生AP,G等位基因频率较高的人可能易患AP。但AA基因型和G等位基因频率不能预测SAP的发生。     

Correlation of estrogen receptor beta gene polymorphisms with spinal bone mineral density in peri- and post-menopausal Greek women

Estrogens play a significant role in bone physiology. Their action is mainly exerted through their receptors. Estrogen receptor alpha (ER) plays a major role in bone homeostasis and there is evidence suggesting that estrogen receptor beta (ERβ) has also an effect on BMD.

We investigated the possible effect of two ERβ gene polymorphisms on spinal bone mineral density (BMD) and metabolic bone markers in Greek women.

Spine BMD as well as biochemical bone markers were measured in 147 healthy peri- and post-menopausal women [mean age (S.D.) 54 (7.9) years]. Genotyping was performed for two restriction fragment length polymorphisms (RFLPs) of ERβ gene, RsaI in exon 5 and AluI in exon 8. For each polymorphism studied the cohort was divided into two groups: the “wild-type” group (RR and AA, respectively) and the “carrier” group including subjects with at least one allele with the restriction site (Rr&rr and Aa&aa, respectively).

The distribution of RsaI genotypes was RR: 91.2% (n = 134), Rr: 8.2% (n = 12), and rr: 0.6% (n = 1) and of AluI genotypes AA: 36.7% (n = 54), Aa: 57.2% (n = 84), and aa: 6.1% (n = 9). No linkage disequilibrium was found between the two polymorphic sites studied. Spine BMD did not differ significantly in the two groups of either polymorphism, after adjusting for age, weight, height, and years since menopause [mean BMD (S.D.) for RR 0.841 (0.17) g/cm² versus Rr&rr 0.798 (0.13) g/cm², p = 0.25, and mean BMD (S.D.) for AA 0.828 (0.16) g/cm² versus Aa&aa 0.848 (0.17) g/cm², p = 0.32]. No significant differences were noted in metabolic bone markers except for a marginal difference of RR versus Rr/rr in urinary hydroxyproline/creatinine ratio [median (IQR) 3.88 (6.04) μmol/mmol in RR versus 8.2 (4.32) μmol/mmol in Rr/rr, p = 0.05]. Furthermore, no interaction between the two polymorphisms on BMD was found.

In conclusion, in a Greek female post-menopausal population, the two ERβ gene polymorphisms were not associated with BMD, or metabolic bone markers.     

Association between EGFR polymorphisms and the risk of lung cancer

Target: The study aimed to investigate the role of epidermal growth factor receptor (EGFR) rs6965469 and rs763317 polymorphisms in the occurrence and development of lung cancer. Methods: We used polymerase chain reaction-ligation detection reaction (PCR-LDR) method to detect the genotypes of EGFR rs6965469 and rs763317 polymorphisms and the data were analyzed by GeneMapper software. Odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by χ² test to estimate the significance difference of genotype and allele frequencies in case and control groups. ORs and 95% CIs were adjusted by logistic regression analysis with age, gender, drinking and smoking. The genotypes distributions of control group were tested by Hardy-Weinberg equilibrium (HWE). Results: The genotypes frequencies of controls for rs6965469 and rs763317 polymorphims were consistent with HWE. The distribution of rs6965469 TT genotype in two groups was significantly different (P<0.05) and TT genotype was associated with an increased risk of lung cancer (OR=6.92, 95% CI=1.33-36.00). AA genotype and A allele of rs763317 were also the susceptible factors of lung cancer. Individuals with AA genotype or A allele were more likely to suffer lung cancer (AA vs. GG: OR=7.20, 95% CI=1.33-39.07; A vs. G: OR=2.61, 95% CI=1.04-6.59). Conclusions: The EGFR rs6965469 and rs763317 polymorphisms may be risk factors for lung cancer.     

CDT1和GMNN基因多态性与女性乳腺癌危险性的关联研究

目的探讨参与DNA复制的两个重要基因CDTI和GMNN基因多态性与我国人群散发乳腺癌的关联。方法采用病例对照研究设计，研究对象包括427例乳腺癌患者及477名无肿瘤史的正常对照组。采用聚合酶链反应-限制性片段长度多态性，方法测定CDT 1838G／A，错配聚合酶链反应-限制性片段长度多态性方法测定GMNN 387C／A的基因型。结果CDT1GG、GA和AA3种基因型以及GMNN CC、CA和从3种基因型在病例组和对照组的频率分布差异无统计学意义（P值分别为0．619和0．793）。然而，分层分析发现，在有肿瘤家族史的人群中，CDT1 GA＋AA基因型可显著增加乳腺癌的危险性（调整OR：2．21，95％CI：1．20～4．09）。结论CDT1 838G／A基因多态性和GMNN 387C／A基因多态性与总的散发性乳腺癌无显著关联，但CDT 1838G／A可能对于具有遗传背景的女性乳腺癌的易感性具有一定的作用。     

DNA修复基因XPC Ala499Val、Lys939Gln多态与肺癌易感性

目的 探讨中国人DNA修复基因XPC Ala499Val、Lys939Gln多态与肺癌易感性的关系。方法 以社区为基础的病例对照研究。经组织学确诊的肺癌病例320例,相同地区年龄和性别频数匹配的人群对照322人,以PER为基础的方法进行多态性检测,比较不同基因型与肺癌风险的关系,并探讨吸烟在其中的影响。结果 与携带499 Ala／Ala基因型者比较,携带至少1个499Val等位基因者（即Ala／Val和Val／Val基因型）肺癌风险增加1．54倍（95％CI=1．11～2．14）,而同时有499和939两个位点变异等位基因者肺癌风险增加2．55倍（95％CI=1．45～4．52）。交互作用分析显示,XPC 499Val变异基因型与吸烟具有超相乘模型的交互作用,同时有两个位点变异等位基因并吸烟者肺癌风险增加可高达7．36倍（95％CI=3．19～17．0）。结论 XPC Ala499Val和Lys939Gln多态可能与中国汉族人群肺癌遗传易感性有关,并可显著增加吸烟对肺癌的危险性。     

Association between HSD17B1 rs605059 polymorphisms and the risk of uterine diseases: a systemic review and meta-analysis

The aim of this study was to evaluate the HSD17B1 gene polymorphisms in the risks of endometrial cancer, endometriosis and uterine leiomyoma by meta-analysis. A comprehensive electronic search was conducted in PubMed, Medline (Ovid), Embase, Weipu, Wanfang and CNKI. The pooled ORs were performed using the Revman 5.2 softerware. 8 case-control studies were included: 3 were about endometrial cancer, 4 were about endometriosis and 1 was about uterine leiomyoma. The result showed no significant association between HSD17B1 rs605059 gene polymorphisms and risks of endometrial cancer (AA vs. AG+GG: OR = 1.11, 95% CI = 0.94-1.32; AA+AG vs. GG: OR = 1.79, 95% CI = 0.42-7.52; AG vs. AA+ GG: OR = 0.87, 95% CI = 0.76-1.00; AA vs. GG: OR = 1.43, 95% CI = 0.62-3.30; A vs. G: OR = 1.00, 95% CI = 0.91-1.11) or endometriosis (AA vs. AG+GG: OR = 0.99, 95% CI = 0.75-1.32; AA+AG vs. GG: OR = 1.73, 95% CI = 0.92-3.25; AG vs. AA+ GG: OR = 1.24, 95% CI = 1.00-1.53; AA vs. GG: OR = 1.54, 95% CI = 0.79-2.97; A vs. G: OR = 1.23, 95% CI = 0.90-1.68). No association was found in a subgroup analysis based on Asian ethnicity for endometriosis. This meta-analysis suggested that HSD17B1 rs605059 polymorphisms were not associated with the risks of endometrial cancer and endometriosis. Further studies are needed to validate the conclusion and clarify the relationship between HSD17B1 rs605059 polymorphisms and the risk of uterine leiomyoma.     

Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer

The tumor suppressor TP53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage and oncogene activation. MDM2 is a key negative regulator of the TP53 pathway and is overexpressed in many cancers as oncoprotein. We investigated the association between genetic variation in the promoter region of MDM2 (c.-5+309G>T, rs2279744:g.G>T) and the coding region of TP53 (c.215G>C, rs1042522:g.G>C, designated Arg72Pro) and the risk of developing lung cancer. The genotypes of 1,106 patients and 1,420 controls were determined by tetra-primer amplification refractory mutation system (ARMS)-PCR or PCR-based restriction fragment length polymorphism (RFLP). Associations with risk of lung cancer were estimated by logistic regression. We observed an increased lung cancer risk associated with the MDM2 GG (odds ratio [OR] = 1.83, 95% confidence interval [CI] = 1.45-2.32) and TG (OR = 1.33, 95% CI = 1.09-1.63) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 1.47, 95% CI = 1.17-1.85, P = 0.003) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased lung cancer risk in a supermultiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 4.56, 95% CI = 2.76-7.54). Significant interactions were observed between these polymorphisms (respectively and jointly) and smoking (OR = 10.41, 95% CI = 5.26-20.58) for smokers with both the MDM2 GG and TP53 Pro/Pro genotypes. In conclusion, genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 contribute to the risk of developing lung cancer.     

Polymorphisms of CYP1A1 and GSTM1 genes and susceptibility to oral cancer

PURPOSE: Oral cancer is the fifth most common form of cancer in the world and comprises 6.5% of all cancer deaths. Since one of the major risk factors for oral cancer is tobacco use, we hypothesized that polymorphic genes coding for tobacco carcinogen-metabolizing enzymes may play a role in oral cancer susceptibility. MATERIALS AND METHODS: To investigate the association between polymorphisms of the CYP1A1 and GSTM1 genes and risks for oral squamous cell carcinoma (OSCC) in the Korean population, the prevalence of the CYP1A1 Mspl and GSTM1 null polymorphisms were examined in 72 patients with histologically confirmed primary OSCC, as well as in 221 healthy control subjects. RESULTS: A significant risk increase for oral cancer was observed among subjects with the homozygous CYP1A1 (m2/m2) genotype (OR=3.8, 95% CI=1.9-7.7), but not the GSTM1 null genotype (OR=0.7, 95% CI=0.4-1.3). Risk for oral cancer was significantly increased in subjects with the homozygous CYP1A1 (m2/m2)genotype, regardless of smoking history (smokers; OR=4.4; 95% CI=1.2-16.3; non- smokers OR=4.9; 95% CI=1.9-12.5). Using the potentially most protective genotype GSTM1 (+)/CYP1A1 [(m1/m1)+ (m1/m2)] as the reference group, an increased risk for oral cancer was observed among subjects with the GSTM1 (+)/ CYP1A1 (m2/m2) (OR= 2.0, 95% CI=0.8-5.2), and GSTM1 (-)/ CYP1A1 (m2/m2) (OR=4.9, 95% CI=1.5-15.5) genotypes (p < 0.009, (chi2 trend test). CONCLUSION: Our results suggest that individuals with a genotype of CYP1A1 (m2/m2) and GSTM1 (-) are highly susceptible for OSCC and that the CYP1A1 (m2/m2) genotype is closely associated with increased risk of OSCC in Koreans.     

Polymorphisms in the caspase-8 gene and the risk of lung cancer

Caspase-8 (CASP-8) is an initiator CASP in the cell death receptor-mediated apoptotic pathway, and plays an important role in the development of cancer. Polymorphisms and their haplotypes in the CASP-8 gene can result in alterations in CASP-8 expression and/or activity, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we examined the association of -678_-673delAGTAAG (-678del) and IVS12-19G-->A polymorphisms and their haplotypes with the risk of lung cancer in a Korean population. The CASP-8 genotypes were determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects. The distributions of the CASP-8 -678del and IVS12-19G-->A genotypes were not significantly different between the overall lung cancer cases and the controls. When the cases were categorized by tumor histology, however, the IVS12-19 AA genotype and the combined IVS12-19 GA + AA genotype were associated with a significantly decreased risk of small cell carcinoma (SmCC) compared with the IVS12-19 GG genotype [adjusted odds ratio (OR) = 0.14, 95% confidence interval (CI) = 0.03-0.64, P = 0.01; and adjusted OR = 0.56, 95% CI = 0.33-0.96, P = 0.03, respectively]. Consistent with the genotyping analyses, the -678del-/IVS12-19A haplotype containing 94% of the IVS12-19A allele in the study population was associated with a significantly decreased risk of SmCC compared with the -678del-/IVS12-19G (adjusted OR = 0.58, 95% CI = 0.36-0.93, P = 0.023, and Pc = 0.046). These findings suggest that the CASP-8 gene may contribute to an inherited predisposition to SmCC of the lung.     

XRCC1 polymorphism and lung cancer risk in relation to tobacco smoking

DNA repair plays a critical role in protecting the genome of the cell from carcinogens or ionising radiation. Reduced DNA-repair capacity can increase susceptibility to occupational-induced cancer. Three coding polymorphisms at codons 194, 280, and 399 in X-ray cross complementing group 1 (XRCC1) DNA-repair gene have been identified, and it is possible that these polymorphisms may affect DNA- repair capacity and thus modulate cancer susceptibility. In the current German study, we investigated the role of XRCC1-polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes, especially in relation to tobacco smoking. Three polymorphisms; XRCC1 Arg194Trp, XRCC1 Arg280His and XRCC1 Arg399Gln, were determined by real-time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients who carried at least one mutant variant allele of XRCC1 Arg194Trp (OR=1.03; 95%-CI: 0.66-1.61), XRCC1 Arg280His (OR=0.95; 95%-CI: 0.57-1.60), or XRCC1 Arg399Gln (OR=0.99 CI: 0.73-1.34), did not show any elevated risks. When analysed by histology, no individual subtype of lung cancer was significantly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption. Stratified analysis between tobacco smoking and variant genotypes revealed increasing risks for heavy smokers (>60 pack-years), with the presence of at least one copy of the XRCC1 Arg194Trp variant allele (OR=79.29; 95%-CI: 8.53-737.04) and the XRCC1 Arg399Gln (OR=61.87; 95%-CI: 15.65-244.67). By analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study, the XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln-polymorphisms, had no relevant modifying effect on lung cancer risk and cumulative smoking dose.     

COX-2启动子区遗传变异与胃癌发病风险的关系

目的 COX-2的过度表达在肿瘤的发生发展中起重要作用,本文探讨COX-2启动子区单核苷酸多态与胃癌易感性的关系。方法以聚合酶链反应-限制性片段长度多态性对155例胃癌患者和237例正常对照进行基因分型,以logistic回归的比值比（OR）及其置信区间（CI）来评估风险度。结果 COX-2-1290AG及GG基因型与胃癌的发病风险无关,OR为1.24（95%CI=0.66-2.35）。而携带COX-2-1195GA或-1195AA基因型的个体胃癌发病风险显著增加,OR分别为1.91（95%CI=1.05-3.47）,2.71（95%CI=1.40-5.27）。单体型分析发现A_1290-A_1195单体型显著增加了胃癌的发病风险（OR=1.49,95%CI=1.10-2.01）。结论 COX-2启动子区-1195G→A遗传变异与胃癌发病风险相关。