Effect of Single Nucleotide Polymorphism Rs189037 in ATM Gene on Risk of Lung Cancer in Chinese: A Case-Control Study

Background

Accumulated evidence has indicated that ataxia-telangiectasia mutated (ATM) gene polymorphisms are closely related to lung cancer. We aimed to explore the prognostic value of rs189037 (G>A), one of ATM single nucleotide polymorphisms (SNPs), and detect whether it involves in the risk of lung cancer in Chinese Han people.

Methods

In this hospital-based matched case-control study, 852 lung cancer patients and 852 healthy controls have been put into comparison to analyze the association between rs189037 and lung cancer risk in Chinese. The single nucleotide polymorphisms were determined by TaqMan real-time PCR and we used SPSS software to perform the statistical analyses.

Results

Individuals carrying variant AA genotype of rs189037 had higher lung cancer risk (adjusted OR: 1.56) than those carrying GG genotype. After analyzing data respectively from different groups divided by genders and smoking status, we observed that the risk effect of AA genotype on the lung cancer was significant in females, non-smokers and female non-smokers, as well as the risk effect of GA genotype in male smokers. Compared with non-smokers carrying GG genotype, smokers carrying at least one A allele had higher risk of developing lung cancer than those with GG genotype (adjusted OR: 3.52 vs. adjusted OR: 2.53).

Conclusions

This study suggested that rs189037 (G>A) polymorphism is associated with lung cancer risk in Chinese Han population. AA genotype and A allele may be dangerous lung cancer signals in Chinese and make contribution to diagnostic and treatment value.     

Distinct Role of CD86 Polymorphisms (rs1129055, rs17281995) in Risk of Cancer: Evidence from a Meta-Analysis

Background and Purpose

Previous studies concerning the role of CD86 polymorphisms (rs1129055 and rs17281995) in cancer fail to provide compelling evidence. The aim of this study was to investigate the role of common polymorphisms in the risk of cancer by meta-analysis.

Methods

By using the search terms Cluster of Differentiation 86/CD86/B7-2/polymorphism/polymorphisms/cancer, we searched PubMed, Embase, CNKI, and Wanfang and identified four studies for rs1129055 (2137 subjects) and rs17281995 (2856 subjects) respectively. Cancer risk was estimated by odds ratio (OR) and 95% confidence interval (95% CI).

Major Findings

Overall, we observed significant reduced risk of cancer in relation to rs1129055. Compared with the individuals with AA genotype, the individuals with GG genotype appeared to have 62% decreased risk to develop cancer (GG versus AA: OR, 0.62; 95% CI, 0.49–0.79; P_het., 0.996). Similar effects were indicated in the G versus A allele model and the GG versus GA+AA genetic model (OR, 0.83; 95% CI, 0.74–0.93; P_het., 0.987; OR, 0.63; 95% CI, 0.50–0.79; P_het., 0.973). In addition, we found genotypes of rs17281995 had a major effect on overall cancer risk (CC versus GG: OR, 2.38; 95% CI, 1.43–3.95; P_het., 0.433; C versus G: OR, 1.23; 95% CI, 1.06–1.43; P_het., 0.521; CC versus GC+GG: OR, 2.38; 95% CI, 1.45–3.93; P_het., 0.443). The association was also observed in Caucasians and colorectal cancer. No obvious publication bias was detected in this meta-analysis.

Conclusions

These data reveal that rs1129055 may have protective effects on cancer risk in Asians and that rs17281995 is likely to contribute to risk of cancer, particularly colorectal cancer in Caucasians.     

A functional +61G/A polymorphism in epidermal growth factor is associated with glioma risk among Asians

Background

Epidermal growth factor (EGF), a potent mitogenic protein, plays an important role in the development of cancers, including glioma. Previous studies showed that the EGF +61G/A polymorphism (rs4444903) may lead to an alteration in EGF production and/or activity, which can result in individual susceptibility to glioma. However, published data regarding the association between the +61G/A polymorphism and glioma risk was contradictory.

Objective

The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the association of EGF +61G/A with glioma risk.

Methods

We performed a pooled analysis of seven published studies that included 1,613 glioma cases and 2,267 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively.

Results

Overall, no significant associations between the EGF +61G/A polymorphism and glioma cancer risk were found for AA versus GG (OR = 0.95, 95% CI = 0.62–1.45), GA versus GG (OR = 0.94, 95% CI = 0.72–1.22), AA/GA versus GG (OR = 0.93, 95% CI = 0.70–1.23), and AA versus GA/GG (OR = 1.04, 95% CI = 0.77–1.39). However, in the stratified analysis by ethnicity, the EGF +61G/A polymorphism had a higher risk of glioma development among Asians, but a lower risk among Caucasians.

Conclusions

Taken together, the results suggest that the EGF +61G/A polymorphism may contribute to the susceptibility of glioma in different ethnic groups.     

Association between CD209 -336A/G and -871A/G Polymorphisms and Susceptibility of Tuberculosis: A Meta-Analysis

Background

The association between CD209 promoter polymorphisms (-336A/G, -871A/G) and tuberculosis (TB) risk has been widely reported, but results of previous studies remain controversial and ambiguous. To assess the association between CD209 polymorphisms and TB risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, we identified outcome data from all articles estimating the association between CD209 polymorphisms and TB risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 14 studies with 3,610 cases and 3,539 controls were identified. There was no significant association between CD209 -336A/G polymorphism and TB risk (OR = 1.04, 95% CI = 0.91–1.19 for G vs. A; OR = 1.13, 95% CI = 0.84–1.53 for GG vs. AA; OR = 1.04, 95% CI = 0.87–1.24 for GG+AG vs. AA; OR = 1.11, 95% CI = 0.88–1.39 for GG vs. AG+AA). However, the significant association was revealed for Asians in GG vs. AA (OR = 2.48, 95% CI = 1.46–4.22, P = 0.0008) and GG vs. AG+AA (OR = 2.10, 95% CI = 1.33–3.32, P = 0.001). For the CD209 -871A/G polymorphism, lack of an association was also found (OR = 0.81, 95% CI = 0.70–0.95 for G vs. A; OR = 1.00, 95% CI = 0.52–1.93 for GG vs. AA; OR = 0.73, 95% CI = 0.60–0.89 for GG+AG vs. AA; OR = 1.09, 95% CI = 0.57–2.10 for GG vs. AG+AA).

Conclusion

The present meta-analysis suggested that CD209 promoter polymorphisms (-336A/G, -871A/G) were unlikely to substantially contribute to TB susceptibility. However, the GG genotype of CD209 -336A/G polymorphism might be a genetic risk factor that increases TB susceptibility for Asians in GG vs. AA and GG vs. AG+AA.     

The -2518A/G Polymorphism in the MCP-1 Gene and Tuberculosis Risk: A Meta-Analysis

Background

The -2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene has been implicated in the susceptibility to tuberculosis (TB), but the results are not conclusive. The aim of this study is to investigate the association between the -2518A/G polymorphism in the MCP-1 gene and the risk of tuberculosis by meta-analysis.

Methods

We searched Pubmed, Embase, CNKI and Wanfang databases, covering all studies until April 29^th, 2011. Statistical analyses were performed using the Revman4.2 and STATA10.0 software.

Results

A total of 5341 cases and 6075 controls in 13 case-control studies were included in the meta-analysis. The results indicated that the GG homozygote carriers had a 67% increased risk of TB compared with the A allele carriers (GG vs. GA+AA: OR = 1.67, 95%CI = 1.25–2.23, P = 0.0006). In the subgroup analysis by ethnicity, significant elevated risks were found in Asians and Latinos, but not in Africans (GG vs. GA+AA: OR = 1.79, 95%CI = 1.19–2.70 and P = 0.005 for Asians; OR = 2.15, 95%CI = 1.32–3.51 and P = 0.002 for Latinos; OR = 1.28, 95%CI = 0.45–3.64 and P = 0.65 for Africans).

Conclusion

This meta-analysis suggested that the -2518A/G polymorphism of MCP-1 gene would be a risk factor for TB in Asians and Latinos, while not in Africans.     

The Leptin Gene Family and Colorectal Cancer: Interaction with Smoking Behavior and Family History of Cancer

Background

Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin.

Methodology/Principal Findings

A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13–1.76) and 1.74 (95%CI 1.08–2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82×10⁻¹⁰).

Conclusions/Significance

Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.     

Tumor Necrosis Factor-A Polymorphisms and Colorectal Cancer Risk: A Meta-Analysis

Background and Objectives

Tumor necrosis factor-alpha (TNF-a) was related to inflammation and involved in the development of colorectal cancer. Polymorphisms located in TNF-a promoter region, such as 308G/A and 238G/A, could affect the risk of various types of cancer by regulating TNF-a production. In this study, a meta-analysis was performed to investigate the association between common polymorphisms of TNF-a promoter region and colorectal cancer susceptibility.

Methods

Searching of several databases was performed for all publications on the association between TNF-a polymorphisms and colorectal cancer. Summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated using random-effects models. Stratified analyses based on ethnicity and control population source were also conducted.

Results

Overall, TNF-a 308A polymorphism showed a significant association with increased risk of colorectal cancer in worldwide populations under homozygote comparison [AA vs. GG, OR (95% CI) = 1.46 (1.07–1.97)] other than heterozygote comparison [AG vs. GG, OR (95% CI) = 1.05 (0.93–1.19)]. TNF-a 238A was not associated with colorectal cancer risk under homozygote or heterozygote comparisons. In stratified analysis, significant association was observed only in Western populations [AA vs. GG, OR (95% CI) = 1.39 (1.01–1.91)] other than in Eastern populations under homozygote comparison. No significant difference was observed between population-based subgroup and hospital-based subgroup.

Conclusions

TNF-a 308A was moderately associated with an increased risk of colorectal cancer in Western populations, and TNF-a 238A polymorphism was not significantly associated with colorectal cancer risk.     

Meta-analysis of TNF 308 G/A polymorphism and type 2 diabetes mellitus

Background and Objectives

Many investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis.

Methods

All publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0.

Results

There were 18 studies identified. The odd ritos (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95–1.12), 1.03 (0.94–1.13) and 1.03 (0.78–1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study.

Conclusion

In summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM.     

Association between MCP-1 -2518A/G Polymorphism and Cancer Risk: Evidence from 19 Case-Control Studies

Background

Single nucleotide polymorphisms (SNPs) may affect the development of diseases. The -2518A/G polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to obtain a more precise estimation of the relationship between the -2518A/G polymorphism and cancer risk.

Methodology/Principal Findings

We performed a meta-analysis, including 4,162 cases and 5,173 controls, to evaluate the strength of the association between the −2518A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Overall, the results indicated that the −2518A/G polymorphism was not statistically associated with cancer risk. However, sub-group analysis revealed that individuals with GG genotypes showed an increased risk of cancer in digestive system compared with carriers of the A allele (GG vs. AA: OR = 1.43, 95%CI = 1.05–1.96, P_{heterogeneity} = 0.08; GG vs. AG/AA: OR = 1.29, 95%CI = 1.02–1.64, P_{heterogeneity} = 0.14). In addition, the increased risk of GG genotype was also observed in Caucasians (GG vs. AG/AA: OR = 1.81, 95%CI = 1.10–2.96, P_{heterogeneity} = 0.02).

Conclusion

This meta-analysis suggests that the MCP-1 −2518A/G polymorphism may have some relation to digestive system cancer susceptibility or cancer development in Caucasian. Large-scale and well-designed case-control studies are needed to validate the findings.     

Increased Risk of Developing Digestive Tract Cancer in Subjects Carrying the PLCE1 rs2274223 A>G Polymorphism: Evidence from a Meta-Analysis

Background

To date, the association between phospholipase C epsilon 1 (PLCE1) rs2274223 A>G and risk of digestive tract cancer (DTC) remains inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis on all eligible case–control studies involving 8281 cases and 10,532 controls.

Methods

A comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and digestive tract cancer risk. The pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using a fixed or random effect model. Heterogeneity, publication bias, and sensitivity analysis were also explored.

Results

Overall, the PLCE1 rs2274223 A>G polymorphism was associated with risk of DTC in all genetic models (GA vs. AA: OR = 1.21, 95% CI = 1.14–1.29, P<0.001; GG vs. AA: OR = 1.30, 95% CI = 1.06–1.60, P = 0.012; GG/GA vs. AA: OR = 1.20, 95% CI = 1.10–1.32, P<0.001; GG vs. GA/AA: OR = 1.21, 95% CI = 1.01–1.46, P = 0.040). The recessive model did not reach statistically significance when the P values were Bonferroni corrected to 0.0125. In the stratified analysis by cancer type, ethnicity, and source of controls, significantly increased risk was observed for esophagus cancer, Asians in three genetic models (heterozygote comparison, homozygote comparison and dominant model), population-based studies in all genetic models, and for gastric cancer in the heterozygote comparison and dominant model after Bonferroni correction. However, in the subsite of gastric cancer, no significant association was found either in cardia or non-cardia gastric cancer.

Conclusion

Our study indicated that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of DTC, especially among Asian populations. Due to some minor limitations, our findings should be confirmed in further studies.     

Relationship between TNF-<alpha> gene promoter polymorphisms and outcomes of hepatitis B virus infections: a meta-analysis

Background

The clearance of hepatitis B virus (HBV) is a complex process which may be influenced by many factors including polymorphisms in the tumor necrosis factor (TNF-) gene promoter. However, previous reports regarding the relationship between polymorphisms in the TNF- promoter and HBV clearance have been inconsistent. Therefore, we performed a meta-analysis on a large population to address this inconsistency.

Methods

A meta-analysis was performed to examine the association between TNF- promoter polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A and-238G/A) and chronic hepatitis B infection. Odds ratio (OR) and its 95 % confidence interval (CI) were used.

Results

Twelve studies were chosen in our meta-analysis, involving 2,754 chronic HBV infection cases and 1,630 HBV clearance cases. The data showed that TNF--863 CC genotype was significantly associated with HBV clearance (-863 CC vs. AA: OR, 0.64; 95% CI, [0.42, 0.97]; p = 0.04) while patients carrying -308 GG genotype had a significantly increased risk of HBV persistence compared with those with GA or AA genotype (GG vs. GA+AA: OR, 1.35; 95% CI, [1.08, 1.70]; p = 0.01). For the other polymorphisms, no association with HBV infection outcome was found.

Conclusions

The data showed that polymorphisms -863 A and -308 G in the TNF- gene promoter region might be risk factors for HBV persistence. Furthermore, ethnicity might play an important role in HBV infection outcome, leading to conflicting results. More studies on individuals from various ethnic groups will be necessary to determine the role of TNF- promoter polymorphisms in the outcome of HBV infection.     

Genetic Variation in BCL2 3′-UTR Was Associated with Lung Cancer Risk and Prognosis in Male Chinese Population

Objectives

Bcl-2 is a critical apoptosis inhibitor with established carcinogenic potential, and can confer cancer cell resistance to therapeutic treatments by activating anti-apoptotic cellular defense. We hypothesized that genetic variants of BCL2 gene may be associated with lung cancer susceptibility and prognosis.

Methods

Three selected tagSNPs of BCL2 (rs2279115, rs1801018, and rs1564483) were genotyped in 1017 paired male Chinese lung cancer cases and controls by TaqMan assay. The associations of these variants with risk of lung cancer and overall survival of 242 male advanced non-small-cell lung cancer (NSCLC) patients were separately investigated.

Results

Compared with the BCL2 3′UTR rs1564483GG genotype, the rs1564483GA, AA, and GA+AA genotypes were associated with significantly decreased susceptibilities of lung cancer in male Chinese (adjusted OR = 0.78, 0.73, and 0.76, P = 0.016, 0.038, and 0.007, respectively), while rs1564483A allele has a inverse dose-response relationship with lung cancer risk (P _trend = 0.010). These effects were more evident in the elders, smokers, and subjects without family history of cancer (P _trend = 0.017, 0.043 and 0.005, respectively). Furthermore, advanced NSCLC males carrying BCL2 rs1564483 GA+AA genotypes had significantly longer median survival time (Long-rank P = 0.036) and decreased death risk (adjusted HR = 0.69, P = 0.027) than patients with rs1564483GG genotype. These effects were more obvious in patients with smoking, stage IIIA, and in patients without surgery but underwent chemotherapy or radiotherapy (adjusted HR = 0.68, 0.49, 0.67, 0.69, 0.50, respectively, all P<0.05).

Conclusion

The BCL2 3′UTR rs1564483A allele was associated with a decreased lung cancer risk and better survival for advanced NSCLC in male Chinese, which may offer a novel biomarker for identifying high-risk population and predicting clinical outcomes.     

IL-10 Gene Polymorphisms and Susceptibility to Systemic Lupus Erythematosus: A Meta-Analysis

Background

A number of observational studies have been conducted to investigate the association of the IL-10 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility. However, their results are conflicting.

Method

We searched published case-control studies on the IL-10 polymorphisms and SLE in PubMed, EMBASE and Chinese Biomedical Literature Database. A meta-analysis was conducted using a fixed-effect or random-effect model based on between-study heterogeneity.

Results

A total of 42 studies with 7948 cases and 11866 controls were included in this meta-analysis. Among Caucasians, the CA27 allele of the IL10.G microsatellites (OR 2.38, 95% CI 1.01–5.62), the G allele of the IL-10 -1082G/A polymorphism (G vs. A: OR 1.21, 95% CI 1.02–1.44; GG vs. AA: OR 1.45, 95% CI 1.16–1.82; GG+GA vs. AA: OR 1.16, 95% CI 1.03–1.29) and its associated haplotype -1082G/−819C/−592C (OR 1.25, 95% CI 1.10–1.42) were associated with increased SLE susceptibility without or with unimportant between-study heterogeneity. Removing studies deviating from Hardy-Weinberg equilibrium (HWE) hardly changed these results. Among Asians, the CA21 allele of the IL-10.G microsatellites (OR 1.28, 95% CI 1.02–1.60) and the -1082G/−819C/−592C haplotype (OR 1.24, 95% CI 1.00–1.53) were associated with increased SLE susceptibility, but with substantial between-study heterogeneity or sensitive to HWE status. Removing studies deviating from HWE also produced statistically significant associations of the IL-10 -1082G/A (GG vs. AA: OR 3.21, 95% CI 1.24–8.28; GG vs. AA+GA: OR 2.85, 95% CI 1.19–6.79) and -592C/A polymorphisms (CC+CA vs. AA: OR 0.69, 95% CI 0.51–0.94) with SLE among Asians.

Conclusion

This meta-analysis showed that the IL10.G microsatellites, the IL-10 -1082G/A and -592C/A polymorphisms and the haplotype -1082G/−819C/−592C are associated with SLE susceptibility. Besides, this is the first time to report an association between the CA27 allele of the IL-10.G microsatellites and SLE among Caucasians. Further studies are needed to confirm these findings.     

A genetic variant in the promoter region of miR-106b-25 cluster and risk of HBV infection and hepatocellular carcinoma

Background

MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response and tumorigenesis. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7.

Methods

We performed a case-control study including 1300 HBV-positive hepatocellular carcinoma (HCC) cases, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the association between rs999885 and the risk of HBV persistent infection and HCC. We also investigated the genotype-expression correlation between rs999885 and miR-106b-25 cluster in 25 pairs of HCC and adjacent non-tumor liver tissues.

Results

Compared with the HBV natural clearance subjects carrying rs999885 AA genotype, those with AG/GG genotypes had a decreased risk of chronic HBV infection with an adjusted odds ratio (OR) of 0.79 [95% confidence intervals (CIs) = 0.67–0.93]. However, the AG/GG genotypes were significantly associated with an increased HCC risk in HBV persistent carriers (adjusted OR = 1.25, 95% CIs = 1.06–1.47). Expression analysis revealed that the expression level of miR-106b-25 cluster was significantly higher in AG/GG carriers than those in AA carriers in non-tumor liver tissues.

Conclusions

These findings indicate that the A to G base change of rs999885 may provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster.     

Single Nucleotide Polymorphism in ATM Gene,Cooking Oil Fumes and Lung Adenocarcinoma Susceptibility in Chinese Female Non-Smokers: A Case-Control Study

Background

The ataxia-telangiectasia mutated (ATM) gene plays an important role in the DNA double-strand breaks repair pathway. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence the risk of lung cancer. This study aimed to investigate the association between the ATM -111G>A (rs189037) polymorphism, environmental risk factors and the risk of lung adenocarcinoma in Chinese female non-smokers.

Methods

A hospital-based case-control study of 487 lung cancer patients and 516 matched cancer-free controls was conducted. Information concerning demographic and environmental risk factors was obtained for each case and control by a trained interviewer. After informed consent was obtained, 10 ml venous blood was collected from each subject for biomarker testing. Single nucleotide polymorphism was determined by using TaqMan method.

Results

This study showed that the individuals with ATM rs189037 AA genotype were at an increased risk for lung adenocarcinoma compared with those carrying the GA or GG genotype (adjusted odds ratios (OR) 1.44, 95% confidence interval (CI) 1.02–2.02, P = 0.039). The stratified analysis suggested that increased risk associated with ATM rs189037 AA genotype in individuals who never or seldom were exposed to cooking oil fumes (adjusted OR 1.89, 95%CI 1.03–3.49, P = 0.040).

Conclusions

ATM rs189037 might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, ATM rs189037 AA genotype might be a risk factor of lung adenocarcinoma among female non-smokers without cooking oil fume exposure.     

A meta-analysis of interleukin-8 -251 promoter polymorphism associated with gastric cancer risk

Background

Potential functional allele A/T single nucleotide polymorphism (SNP) of Interleukin 8 (IL-8) promoter -251has been implicated in gastric cancer risk.

Methods

We aimed to explore the role of A/T SNP of IL-8 -251 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Eighteen studies were ultimately eligible for the meta-analysis of IL-8 - 251 A/T SNP. We adopted the most probably appropriate genetic model (codominant model). Potential sources of heterogeneity were sought out via stratification and sensitivity analyses, and publication biases were estimated.

Results

Between IL-8 -251 AA genotype with gastric cancer risk, statistically significant association could be noted with overall gastric cancer, evidently noted in Asians, witnessed in high quality subgroup, and apparently noted in intestinal-type gastric cancer.

Conclusions

Our meta-analysis indicates that IL-8 -251 AA genotype is associated with the overall risk of developing gastric cancer and may seem to be more susceptible to overall gastric cancer in Asian populations. IL-8 -251 AA genotype is more associated with the intestinal-type gastric cancer. IL-8 -251 AA genotype is not associated with Helicobacter Pylori infection status in our meta-analysis.

Impact

The analyses suggest that IL-8 -251 AA genotype may be an important biomarker of gastric cancer susceptibility for Asians, especially for Chinese Han population, the assumption that needs to be further confirmed in future well-designed studies in China.     

Functional Polymorphisms of FAS and FASL Gene and Risk of Breast Cancer – Pilot Study of 134 Cases

Fas/Fas ligand (FasL) system is one of the key apoptotic signaling entities in the extrinsic apoptotic pathway. De-regulation of this pathway, i.e. by mutations may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between −1377 G/A (rs2234767) and −670 A/G (rs1800682) polymorphisms in Fas as well as single nucleotide polymorphisms INV2nt −124 A/G (rs5030772) and −844 C/T (rs763110) in FasL in a sample of Iranian patients with breast cancer. This case-control study was done on 134 breast cancer patients and 152 normal women. Genomic DNA was extracted from whole blood samples. The polymorphisms were determined by using tetra-ARMS-PCR method. There was no significant difference in the genotype distribution of FAS rs2234767 polymorphism between cases and controls. FAS rs1800682, FASL rs5030772, and FASL rs763110 genotypes showed significant associations with an increasing risk of breast cancer (odds ratio OR = 3.18, P = 0.019; OR = 5.08, P = 0.012; OR = 2.40, P = 0.024, respectively). In conclusion, FAS rs2234767 was not associated with breast cancer risk. Though, FAS rs1800682, FASL rs5030772, and FASL rs763110 polymorphisms were associated with the risk of breast cancer in the examined population.