Interaction of cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer

Overexpression of cyclooxygenase (COX)-2 has been implicated in the development of cancer. This study aimed to evaluate the relationship between genetic variants in COX-2 promoter interacting with Helicobacter pylori and the susceptibility to gastric cancer (GC). Three COX-2 polymorphisms -1290A>G (rs689465), -1195G>A (rs689466), and -765G>C (rs20417) were genotyped in 323 GC patients and 944 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. In GC patients, the ORs were 2.33 (95% CI = 1.50-3.63) and 2.70 (95% CI = 1.68-4.33) for -1195AA and -765CG genotype carriers, respectively. Haplotype analysis showed all -1195A allele-containing haplotypes, except G(-1290)-A(-1195)-G(-765), were associated with increased risk for GC, compared with the A(-1290)-G(-1195)-G(-765) haplotype. Moreover, significant multiplicative and additive interactions were observed between H. pylori infection and all these three polymorphisms, and H. pylori-infected subjects carrying the variant allele of -1290A>G, -1195G>A, or -765G>C had increased risk of GC compared with non-H. pylori-infected subjects with wild-type allele (OR = 4.10, 95% CI = 1.90-8.83; OR = 3.46, 95% CI = 1.31-9.11; and OR = 3.32, 95% = 1.27-8.73, respectively). Our results suggested that the COX-2 promoter polymorphisms were associated with increased risk of GC, especially interacting with H. pylori infection.     

The 765G>C Polymorphism in the Cyclooxygenase-2 Gene and Gastric Cancer Risk: an Update by Meta-analysis

Background: The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigatedfor association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aimof this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene forGC. Materials and Methods: We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipudatabase, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10,2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. Results: A total of 1,874cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated thatthe variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG(odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis byethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18,and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07,95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysisby Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58,95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). Conclusions:This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GCin Asians and Indians.     

Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer

Aberrant arachidonic acid metabolism by cyclooxygenase (COX)-2 and 12-lipoxygenase (LOX) has implicated in carcinogenesis. Genetic polymorphisms in COX-2 and 12-LOX might therefore affect susceptibility to colorectal cancer (CRC). To examine this hypothesis, genotypes of COX-2 -1290A>G, -1195G>A, -765G>C and 12-LOX 261Arg>Gln polymorphisms were determined in 1000 CRC patients and 1300 controls. Increased risk of developing CRC was associated with the COX-2 -1195GA [adjusted odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.00-1.54] and -1195AA (adjusted OR = 1.77, 95% CI = 1.38-2.25) genotypes compared with the -1195GG genotype. Similarly, the increased risk for CRC was also associated with the COX-2 -765GC genotype (adjusted OR = 1.73, 95% CI = 1.23-2.43) compared with the -765GG genotype. Consistent with the results of genotype analyses, the ORs for the A_(1195)-C_(765)-containing haplotypes were significantly higher than those for the G_(1195)-G_(765)-containing haplotypes (P < 0.01). Furthermore, the -1195A allele was further associated with advanced CRC, with adjusted ORs of Dukes D CRC against Dukes A CRC being 2.43 (95% CI = 1.15-4.97) and 2.66 (95% CI = 1.23-5.74) for the -1195GA and -1195AA genotypes, respectively. The increased risk of CRC was also associated with the 12-LOX 261Gln/Gln genotype compared with the Arg/Arg genotype (adjusted OR = 1.38, 95% CI = 1.09-1.74). Together, these observations indicate that inherited polymorphisms in arachidonic acid-metabolizing enzymes may confer susceptibility to CRC.     

The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis

Background: Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2(COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensivelyevaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. Materialsand Methods: A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBMdatabases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. Results:A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. Theresults indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer whencompared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CCvs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers(GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, andp< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type(GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk forgastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophagealcancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in thenpopulation-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC)studies. Conclusions: This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is apotential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.     

Association of Cytotoxic T-lymphocyte Antigen-4 Polymorphisms with Malignant Bone Tumors Risk A Meta-analysis

Background Previous studies have assessed the association between the Cytotoxic T-lymphocyte Antigen- 4(CTLA-4) polymorphism with the risk of malignant bone tumor, but the conclusions were inconsistent. We aimed to clarify association of cytotoxic T-lymphocyte antigen-4 polymorphisms with malignant bone tumors risk by performing a meta-analysis. Materials and Methods The databases including PubMed, EMBase databases and the Cochrane Library were searched to identify the eligible studies prior to January 30 2016. Odds ratio (OR) with 95% con dence interval (95%CI) were used to estimate the strengths of the association between the CTLA-4 polymorphism and the malignant bone tumor risks. The meta-analysis was performed by STATA 12.0. Results Four individual studies with a total of 1003 cases with malignant bone tumor and 1162 controls were included in our meta-analysis. The results of meta-analysis on those data demonstrated that CTLA-4 +49G>A polymorphism was associated with the risk of Ewing's sarcoma and osteosarcoma strongly (A vs. G OR1.36, 95%CI1.20- 1.54, p0.000; AA+AG vs. GG OR1.35, 95%CI1.14-1.61, p0.001; AA vs. GG OR2.24, 95%CI1.67-2.99, p0.000; AA vs. AG+GG OR2.00, 95%CI1.53-2.62, p0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumor (C vs. T OR0.76, 95%CI0.76-1.08, p 0.262; CC+CT vs. TT OR0.70, 95%CI0.41-1.20, p0.198; CC vs. TT OR0.69, 95%CI0.40-1.19, p 0.183; CC vs. CT+TT OR0.92, 95%CI0.75-1.13, p 0.419). Subgroup analysis showed that there are signi cantly positive correlations between CTLA-4 +49G>A polymorphism and increased risks of malignant bone tumors in large size of sample (A vs. G OR1.347, 95%CI 1.172,1.548, p0.000; AA vs. GG OR2.228, 95%CI 1.608,3.085, p0.000), Ewing's Sarcoma or Osteosarcoma (A vs. G OR1.361, 95%CI 1.201,1.540, p0.000; AA vs. GG OR2.236, 95%CI 1.674,2.986, p0.000), and PCR-RFLP or Sequencing(A vs. G OR1.361, 95%CI 1.201,1.540, p0.000; AA vs. GG OR2.236, 95%CI 1.674,2.986, p0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumors in diagnosis, genotype method, and sample size (all p>0.05). Conclusions CTLA-4 +49A/G variant was associated with an increased risk of developing the malignant bone tumors, such as Ewing's sarcoma and osteosarcoma. However, it failed to show the association between CTLA-4 -318C/T polymorphism and the risk of malignant bone tumors. Future large-scale studies remain to be done to con rm our conclusions.     

The COX-2 -765 G>C Polymorphism is Associated with Increased Risk of Gastric Carcinogenesis in the Chinese Hui Ethnic Population

Background: The Chinese Hui ethnic group has diverse origins, including Arab, Persian, Central Asian,and Mongol. The standardized mortality rate of gastric cancer in the Hui population is higher than the overallChinese population. In this study, we investigated whether COX-2-765G>C polymorphism, an extensively studiedpolymorphism, contributes to gastric cancer and its precursor lesions (GPL) in the Chinese Hui ethnic group.Materials and Methods: COX-2-765G>C polymorphism was determined by pyrosequencing in 100 gastriccancer cases, 102 gastric cancerand its precursor lesions cases and 105 controls. Data were statistically analyzedusing Chi-square tests and logistic regression models. Results: Among the Chinese Hui ethnic group COX-2-765 C allele carriers were at increased risk for gastric cancer (OR=1.977, 95%CI=1.104-3.541). We also foundan interaction between COX-2 -765 C carriers and Helicobacter pylori infection and eating pickled vegetables.Conclusions: Our findings suggest a multi-step process of gene-environment interaction contributes to gastriccarcinogenesis.     

Genetic polymorphisms of cyclooxygenase-2 and colorectal adenoma risk: the Self Defense Forces Health Study

Cyclooxygenase (COX) is a key enzyme in the formation of prostaglandins, and an inducible isoform of COX, COX-2, has been implicated in colorectal carcinogenesis. This study investigated the relation of COX-2 polymorphisms (–1195G>A, –765G>C and 8160A>G) to colorectal adenomas in a case–control study of male officials in the Self Defense Forces (SDF). The study subjects were 455 cases of colorectal adenoma and 1052 controls with no polyps who underwent total colonoscopy. Genotypes were determined using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index (BMI), cigarette smoking, and alcohol intake. A statistically non-significant decrease in the risk of colorectal adenomas was observed for the AA versus GG genotype of –1195G>A polymorphism and for the GC versus GG genotype of –765G>C polymorphism. None had the –765CC genotype in either the case or control groups. No effect modification of overweight, smoking or alcohol use was observed for either –1195G>A or –765G>C polymorphism. The variant allele of the 8160A>G polymorphism was extremely rare. A haplotype of –1195G, –765G and 8160A alleles was associated with a modest increase in the risk (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] 0.99–1.91), and the increase was more evident for distal adenomas (adjusted OR 1.57, 95% CI 1.04–2.38). Another haplotype of –1195A, –765C and 8160A alleles showed an adjusted OR of 0.22 (95% CI 0.06–0.88). These findings add to evidence for the role of COX-2 in colorectal carcinogenesis and warrant further studies focusing on haplotypes. ( Cancer Sci 2008; 99: 576–581)     

Risk assessment of p53 genotypes and haplotypes in tobacco-associated leukoplakia and oral cancer patients from eastern Idia

The role of 3 p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and intron 6 NciI RFLP at np 13494) as potential markers for indicating cancer risk remains inconclusive. In our case-control study consisting of 197 leukoplakia and 310 oral squamous cell carcinoma (SCC) patients and 348 controls, genotype frequencies at these 3 p53 loci were determined by PCR-RFLP method and analyzed by multiple logistic regression to determine the risks of the diseases. The 2/2 genotype at codon 72 of p53 was at risk for developing leukoplakia (OR = 1.6, 95% CI 1.1-2.3), whereas the combination of 1/2 and 2/2 genotypes at intron 3 and 1/1 and 1/2 genotypes at intron 6 conferred a protective effect against leukoplakia and oral SCC development, respectively (OR = 0.5, 95% CI 0.4-0.8 and OR = 0.6, 95% CI 0.5-0.9, respectively). When subjects were stratified according to specific tobacco habit, the risk/protection estimates improved significantly in some cases. Specifically, the exclusive smokers with p53 codon 72 2/2 genotype showed a higher risk of developing leukoplakia (OR = 2.7, 95% CI 1.2-6.3). Furthermore, a particular p53 haplotype 1-2-2 was at risk for both tobacco-associated leukoplakia and oral SCC (OR = 1.5, 95% CI 1.1-1.9 and OR = 1.3, 95% CI 1.1-1.7, respectively). Our results show that both specific p53 genotype and haplotype can indicate risk of tobacco-associated leukoplakia, but risk of development of tobacco-associated oral SCC can be predicted by specific p53 haplotype only.     

Tumor Necrosis Factor-α Gene Polymorphisms and Risk of Oral Cancer: Evidence from a Meta-analysis

Numerous studies have been conducted regarding association between TNF-α and oral cancer risk, but theresults remain controversial. The present meta-analysis is performed to acquire a more precise estimation ofrelationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI)were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) werecalculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test.Among the eight included case-control studies, all were focused on TNF-α-308G>A and four also concernedthe TNF-α-238G>A polymorphism. It was found that oral cancer risk were significant decreased with theTNF-α-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00],P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03,I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23,2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41,I2=93.1%). For the TNF-α-238G>A polymorphism, significant associations with oral cancer risk were found inthe allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GGvs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates thatTNF-α polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-α-308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-α-238G>A may causean increase.     

Association of IL-6 -174G>C and -572G>C Polymorphisms with Susceptibility to Cervical Cancer and Ovarian Cancer

Background: During the past decades, the expansion of molecular development has had a key role in understanding the basis of gynecological cancer. Interleukin-6 (IL-6) is known to be involved in the pathogenesis of different cancers. Here, we evaluated the association of IL-6 -174G>C and -572 G>C polymorphisms with susceptibility to cervical and ovarian cancers in an Iranian population. Methods: A total of 131 cases with ovarian cancer, 124 cases with cervical cancer and 140 healthy subjects were enrolled to the study. DNA was extracted from peripheral blood cells of subjects to genotype the IL-6 -174G>C and -572 G>C polymorphisms by amplification refractory mutation system (RFLP) polymerase chain reaction (PCR). Results: There was a significant association of IL-6 -174G>C CC genotype (OR= 3.231, 95% CI: 1.130-9.239, p=0.029) and C allele (OR = 1.915; 95%CI: 1.266-2.896, p=0.002) with an increased risk of ovarian cancer. Moreover, the IL-6 -174G>C CC genotype (OR= 3.162, 95% CI: 1.094-9.141, p=0.034) and C allele (OR = 1.724; 95%CI: 1.129-2.633, p=0.012) was associated with increased risk of cervical cancer. Conclusions: This study showed that the IL-6 -174G>C polymorphism was associated with ovarian cancer and cervical cancer risk. However, IL-6 -572 G>C polymorphism was not associated.     

TP53 (rs1042522, rs28934571) and TP21 (rs1801270, rs1059234) Polymorphisms and Risk of Breast Cancer among Rural Women of Maharashtra: Findings from a Hospital Based Case- Control Study

Background: Various studies all around the world depicted the relationship of polymorphisms in tumor suppressor genes with risk of various cancers, but there are unambiguous conclusions on this association. A hospital based case-control study was designed to review the association of polymorphism of tumor suppressor genes p21 and p53 with breast cancer risk in women residing in rural Maharashtra. Methods: Two single nucleotide polymorphisms (SNPs) a C>A transversion (Ser>Arg) at codon 31 of exon 2 (rs1801270), C>T transition occurring 20bp upstream from stop codon of exon 3 (rs1059234) in p21 gene and G>C (Arg>Pro) transition at codon 72 of exon 4 (rs1042522), G>T (Arg>Ser) transition at codon 249 in exon 7 (rs28934571) in p53 gene were studied. To precise the quantitative assessment, we enrolled 800 subjects sorted into 400 clinically confirmed breast cancer patients and 400 healthy women from a tertiary care hospital (Krishna Hospital and Medical Research Centre) of south-western Maharashtra. The genetic polymorphisms in p21 and p53 genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using blood genomic DNA isolated from breast cancer patients and controls.  The level of association of polymorphisms was assessed using Odds ratio (OR) with 95% confidence interval and p-value identified using logistic regression model. Results: After the analysis of SNPs (rs1801270, rs1059234) of p21 and (rs1042522, rs28934571) in p53 gene our analysis suggested that heterozygote Ser/Arg genotype with OR=0.66; 95% CI: 0.47- 0.91; p=0.0003 and homozygote variant Arg/Arg genotype with OR=0.23; 95% CI: 0.13- 0.40; p<0.0001of rs1801270 of p21 was negatively associated with risk of breast cancer in studied population. Conclusion: The findings from this study supported that rs1801270 SNP of p21 was inversely associated with breast cancer risk in the studied rural women population.     

P53 Codon 72 polymorphisms: a case-control study of gastric cancer and potential interactions

P53 codon 72 polymorphisms have been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the interaction of select risk factors and p53 codon 72 polymorphisms in gastric cancer susceptibility. 155 gastric cancer cases and 134 cancer-free controls were enrolled at the Memorial Sloan Kettering Cancer Center (MSKCC) from November 1992 to November 1994. The crude odds ratio (OR1) associated with the (Pro/Pro) polymorphism and the risk of gastric cancer was 1.27 (0.70-2.33). Adjusting for age, sex, race and education (OR2) and further adjusting for BMI, calories, sodium, smoking, vitamin C, fiber, alcohol, fat, and H. pylori status (OR3) did not yield significant results. Significant joint effects were associated with high fat consumption (OR1=2.61 (95% CI:1.13-6.06); OR2=2.85 (95% CI:1.14-7.15) for total cancers and for proximal tumors (OR1=2.56 (95%CI:1.00-6.54)). The low vitamin C intake/high-risk polymorphism group (Pro/Pro) had an OR1 of 4.82 (95% CI: 1.72-13.45) and the OR2 was 6.19 (95% CI: 2.08-18.40) for distal tumors. The point estimates were increased for interaction odds ratios but not statistically significant (OR1=4.25 (95% CI: 0.66-27.50); OR2=4.73 (95% CI: 0.67-33.43); OR3=5.55 (95% CI: 0.66-46.47)). Further studies specifically looking at proximal and distal tumors are required to confirm any potential interaction between the p53 codon 72 polymorphisms and environmental risk, in particular low dietary vitamin C and high fat consumption.     

MDM2 and TP53 Polymorphisms as Predictive Markers for Head and Neck Cancer in Northeast Indian Population: Effect of Gene-Gene and Gene-Environment Interactions

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increasethe susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also stronglyassociated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In acase-control study, we investigated the significance of the above polymorphisms alone, and upon interaction withone another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population.Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthycontrols was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing.Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to thosewith the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in femalesby ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone;however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95%CI: 0.2-105.1) (p=0.04). Smokers, BQ- chewers and alcohol consumers showed statistically significant and dosedependentincrease in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serveas an important predictive biomarker for HNC risk in the population of Northeast India.     

DNA修复基因XPD XPC XRCC4基因多态性与结直肠癌易感性的关联性研究

  目的  探讨DNA修复基因XPD rs13181（codon751A/C,Lys751Gln）、rs238406（codon156C/A,Arg156Arg）、XPC rs2279017（i11C/A）和XRCC4 rs3734091（codon247T/C,Ala247Ser）的单核苷酸多态性与结直肠癌易感性的关系。  方法  采用TaqMan技术对2013年4月至2016年1月北京肿瘤医院收治的338例结直肠癌患者（病例组）和315例健康者（对照组）进行多态位点基因型的检测。  结果  XPD rs13181基因型GT和等位基因G增加个体结直肠癌的发病风险（GT>TT,adjusted OR=1.69,95%CI:1.15~2.47,P=0.007;G>T,adjusted OR=1.77,95%CI:1.19~2.64,P=0.005）;XRCC4 rs3734091基因型GT和等位基因T增加个体结直肠癌的易感性（GT>GG,adjusted OR=9.02,95%CI:5.61~14.50,P＜0.001;T>G,adjusted OR=4.06,95%CI:2.49~6.61,P＜0.001）;XPD rs13181和rs238406的单倍体型GT显著降低结直肠癌的发病风险（adjusted OR=0.39,95%CI:0.18~0.85,P=0.018）。XPCrs2279017等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=28.43,95%CI:6.85~117.95,P＜0.001）以及XPD rs13181等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=10.24,95%CI:4.69~22.35,P＜0.001）显著增加个体结直肠癌的易感性。  结论  XPD rs13181和XRCC4 rs3734091位点的多态性与结直肠癌的易感性相关。      

鼠双微体同源基因2遗传多态与结直肠癌患病风险的相关性

目的 探讨p53 72 Arg→Pro和鼠双微体同源基因2(MDM2) 309 T→G多态与结直肠癌(CRC)发生发展的关系.方法 采用病例-对照关联研究方法,分析1000例CRC和1300例正常对照中p53 72 Arg→Pro和MDM2 309 T→G的基因型.以多因素Logistic回归模型计算各基因型的比值比(OR)及其95%可信区间(CI).结果 携带MDM2 309 GG或TG基因型者患CRC的风险比TT基因型者显著增高,OR分别为2.06(95%CI为1.62～2.62)和1.31(95%CI为1.06～1.62).p53 72 Arg→Pro多态与CRC风险不相关.两个基因多态联合分析表明,既携带MDM2 309 GG,又携带p53 72 Pro/Pro基因型者,患CRC的OR显著高于携带MDM2 309 TT和p53 72 Pro/Pro基因型者[2.75(95%CI为1.60～4.70)比1.09(95%CI为0.63～1.88);χ2=9.83,P=0.002].结论 MDM2基因的遗传多态可能是CRC的遗传易感性因素.     

Demographic Risk Factors,Affected Anatomical Sites and Clinicopathological Profile for Oral Squamous Cell Carcinoma in a North Indian Population

Background: Oral cancer is a common form of cancer in India, particularly among men. About 95% are squamous cell carcinomas. Tobacco along with alcohol are regarded as the major risk factors. Objectives: (i) To determine associations of oral squamous cell carcinoma (OSCC) with respect to gender, age group, socioeconomic status and risk habits; (ii) To observe the distribution of affected oral anatomical sites and clinico-pathological profile in OSCC patients. Materials and Methods: This is an unmatched case-control study during period January 2012 to December 2013. Total of 471 confirmed OSCC patients and 556 control subjects were enrolled. Data on socio-demography, risk habits with duration and medical history were recorded. Results: There were significant associations between OSCC with middle age (41-50years; unadjusted OR=1.63, 95%CI=1.05-2.52, p=0.02) (51-60 years; unadjusted OR=1.79, 95%CI=1.15-2.79, p=0.009) and male subjects (unadjusted OR=2.49, 95%CI=1.89-3.27, p=0.0001). Cases with both habits of tobacco chewing and smoking were at a higher risk for OSCC than tobacco chewing alone (unadjusted OR=0.52, 95%CI=0.38-0.72, p=0.0001), duration of risk habits also emerged as a responsible factor for the development of carcinoma. The majority of patients were presented in well-differentiated carcinomas (39.9%). Prevalence of advance stages (TNM stage III, IV) was 23.4% and 18.3% respectively. The buccal mucosa was the most common (35.5%) affected oral site. Conclusions: In most Asian countries, especially India, there is an important need to initiate the national level public awareness programs to control and prevent oral cancer by screening for early diagnosis and support a tobacco free environment.     

Cyclooxygenase‐2 gene polymorphisms reduce the risk of oral premalignant lesions

BACKGROUND:

Oral premalignant lesions (OPLs) have the potential to transform into malignant oral cancers. Overexpression of the cyclooxygenase‐2 gene (COX‐2) is observed frequently in OPLs and oral cancers, suggesting that this gene may play an important role in the progression of oral cancer. Single‐nucleotide polymorphisms of COX‐2 have been associated with the risk of multiple cancers; however, to date, their effects on OPL susceptibility have not been evaluated sufficiently.

METHODS:

The authors conducted a case‐control study that included 147 patients with OPL and a group of 147 healthy, matched controls. The effects of 3 potentially functional COX‐2 polymorphisms on the risk of OPL were evaluated: the ?765 G→C polymorphism (rs20417), the exon 10 +837 T→C polymorphism (rs5275), and the exon 10 ?90 C→T polymorphism (rs689470).

RESULTS:

The variant‐containing genotypes of COX‐2 exon 10 +837T→C variant were associated with a significantly reduced risk of OPL (odds ratio [OR], 0.48; 95% confidence interval [95% CI], 0.28‐0.80). This protective effect also was significant in men, younger individuals, ever smokers, and ever drinkers. Consistently, a common halotype WMW (in the following order: ?765G→C, exon 10 +837T→C, and exon 10 ?90C→T; w, widetype; M, variable allele) and a common diplotype (WWW/WMW) that contained the variant allele of exon 10 +837T→C, both were associated with a reduced risk of OPL (WMW: OR, 0.55; 95% CI, 0.33‐0.93; WWW/WMW: OR, 0.44; 95% CI, 0.22‐0.89). In addition, using never smokers with the variant‐containing genotypes as the reference group, interaction effects were observed between specific COX‐2 variants and tobacco smoking in the modulation of OPL risk.

CONCLUSIONS:

Overall, the current results provided the first epidemiologic evidence indicating that potentially functional polymorphisms of the COX‐2 gene may have an impact on individual susceptibility to OPLs. Cancer 2009. © 2009 American Cancer Society.