Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis

Background

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

Methods

We firstly performed a hospital-based case-control study involving 165 NPC cases and 191 cancer-free controls in central-south China, and then conducted a meta-analysis with six case-control studies to evaluate the association between NPC risk and CCND1 G870A polymorphism.

Results

The case-control study found a significant association between CCND1 G870A polymorphism and NPC risk in various comparison models (AA vs. GG: OR = 2.300, 95% CI 1.089–4.857, p = 0.029; AG vs. GG: OR = 2.832, 95% CI 1.367–5.867, p = 0.005; AA/AG vs. GG: OR = 2.597, 95% CI 1.288–5.237, p = 0.008; AA vs. AG/GG: OR = 0.984, 95% CI 0.638–1.518, p = 0.944). Further meta-analysis showed that there was no significant association between CCND1 G870A polymorphism and NPC risk in overall analysis. In the stratified analysis by race, however, significant associations were only found in Caucasians (for the allele model A vs. G: OR = 0.75, 95% CI 0.59–0.97, p = 0.03; for the co-dominant model AA vs. GG: OR = 0.52, 95% CI 0.32–0.86, p = 0.01; for the dominant model AA/AG vs. GG: OR = 0.49, 95% CI 0.32–0.74, p<0.01; for the recessive model AA vs. AG/GG: OR = 0.90, 95% CI 0.61–1.34, p = 0.60).

Conclusions

A significant association between CCND1 G870A polymorphism and NPC risk was found in the central-southern Chinese population. The meta-analysis indicated that CCND1 G870A polymorphism may contribute to the development of NPC in Caucasians.     

Potential role of CCND1 G870A genotype as a predictor for urothelial carcinoma susceptibility and muscle-invasiveness in Taiwan

The cell cycle regulator cyclin D1 (CCND1) is thought to play a major role in the transition of cell cycle from G1 to S phase. It is known that a common CCND1 G870A genotype is associated with bladder cancer in Japan and China, but not in the Western World. There is neither a report about its role in Taiwan's population, nor its genetic role of CCND1 G870A in another worldwide urothelial cancer, upper tract urothelial cancer (UTUC). Therefore, we aimed at investigating the role of CCND1 G870A in both bladder cancer and UTUC in Taiwanese cohorts. The CCND1 G870A genotypes of 171 (101 bladder cancer and 70 UTUC) patients and 243 control subjects were determined by PCR-RFLP and their correlation with clinical and histopathological data was evaluated. The genotype analysis results showed that CCND1 GG genotype was associated with a lower risk overall in urothelial (P = 0.008, OR = 0.44, 95% CI = 0.24-0.81) and bladder cancer patients (P = 0.008, OR = 0.34, 95% CI = 0.15-0.76) than those of the AA genotype. In addition, patients carrying the AG genotype had a 0.29-fold lower odds ratio of muscle-invasive cancer procession (95% CI = 0.12-0.70) compared with those carrying the AA genotype in bladder cancer patients. Surprisingly, the GG genotype had a 5.88-fold higher odds ratio of muscle-invasive cancer procession (95% CI = 1.08-32.01) compared with those carrying the AA genotype in UTUC. No association between any CCND1 G870A genotype and higher-grade risk was found. Our results suggest that the G allele of the CCND1 G870A polymorphism may be a potential predictive and prognostic biomarker to distinguish between bladder cancer and UTUC in Taiwan.     

CCND1 G870A polymorphism interaction with cigarette smoking increases lung cancer risk: meta-analyses based on 5008 cases and 5214 controls

Evidence indicates CCND1 G870A polymorphisms as a risk factor for a number of cancers. Increasing studies have been conducted on the association of CCND1 G870A polymorphism with lung cancer risk. However, the results were controversial. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses examining the association between CCND1 G870A polymorphism and lung cancer were performed. Subgroup analyses regarding ethnicity, smoking status, histological types and source of controls were also implemented. All eligible studies for the period up to May 2012 were identified. The overall data from ten case–control studies including 5,008 cases and 5,214 controls indicated that variant A allele may have an association with increased lung cancer risk (AA vs GG: OR = 1.21; 95 % CI = 1.08–1.36, dominant model: OR = 1.09; 95 % CI = 1.00–1.19, recessive model: OR = 1.23; 95 % CI = 1.01–1.49). In the subgroup analysis by ethnicity, A allele may elevate lung cancer risk among Asians but not Caucasians or Mixed ethnicities. In smoking status subgroup, A allele was shown to associate with increased lung cancer risk among smokers but not non-smokers. In the subgroup analysis by histological types, increased cancer risks were shown in adenocarcinoma but not squamous cell carcinoma, under the homozygote comparison and recessive models. Collectively, the results of the present study suggest that CCND1 G870A polymorphism might be a low-penetrant risk factor for lung cancer, particularly among Asians and smokers. Moreover, homozygous AA alleles might have a correlation with increased lung adenocarcinoma susceptibility.     

The polymorphisms in methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase, and the risk of colorectal cancer

Polymorphisms in genes involved in folate metabolism may modulate the risk of colorectal cancer (CRC), but data from published studies are conflicting. The current meta-analysis was performed to address a more accurate estimation. A total of 41 (17,552 cases and 26,238 controls), 24(8,263 cases and 12,033 controls), 12(3,758 cases and 5,646 controls), and 13 (5,511 cases and 7,265 controls) studies were finally included for the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1289C, methione synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G polymorphisms and the risk of CRC, respectively. The data showed that the MTHFR 677T allele was significantly associated with reduced risk of CRC (OR = 0.93, 95%CI 0.90-0.96), while the MTRR 66G allele was significantly associated with increased risk of CRC (OR = 1.11, 95%CI 1.01-1.18). Sub-group analysis by ethnicity revealed that MTHFR C677T polymorphism was significantly associated with reduced risk of CRC in Asians (OR = 0.80, 95%CI 0.72-0.89) and Caucasians (OR = 0.84, 95%CI 0.76-0.93) in recessive genetic model, while the MTRR 66GG genotype was found to significantly increase the risk of CRC in Caucasians (GG vs. AA: OR = 1.18, 95%CI 1.03-1.36). No significant association was found between MTHFR A1298C and MTR A2756G polymorphisms and the risk of CRC. Cumulative meta-analysis showed no particular time trend existed in the summary estimate. Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test. Collectively, this meta-analysis suggested that MTHFR 677T allele might provide protection against CRC in worldwide populations, while MTRR 66G allele might increase the risk of CRC in Caucasians. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.     

Cyclin D1 (G870A) polymorphism and risk of cervix cancer: a case control study in north Indian population

Cyclin D1 (CCND1) is a key regulatory protein, playing a critical role in the transition from G1 to S phase of the cell cycle. We have evaluated the association between CCND1 A870G polymorphism and risk of cervix cancer in north Indian women by using PCR-RFLP method. This association was estimated by computing odds ratio (ORs) and a 95% Confidence Intervals (95% CI) using a Multivariate Logistic Regression Analysis. No significant association was observed between CCND1 genotypes and overall risk of cervix cancer. But when stratified histologically, statistically significant (OR: 3.7, 95% CI: 1.56-8.87, P: 0.001) increased risk of squamous cell carcinoma (SCC) was observed for individuals with AA genotype. Thus our findings suggest that CCND1 (G870A) polymorphism may be associated with increased risk of SCC of the uterine cervix in north Indian women.     

Cyclin D1 G870A polymorphism and breast cancer risk: a meta-analysis comprising 9,911 cases and 11,171 controls

Cyclin D1 represents a key molecule in the regulation of cell cycle. CCND1 G870A (rs603965) polymorphism has drawn considerable attention as the A allele may generate a variant splice product with possible oncogenic actions. A meta-analysis examining the association between CCND1 G870A polymorphism and breast cancer risk was performed. Separate analyses on Caucasian and Chinese populations were also implemented. Eligible articles were identified for the period up to July 2010. Pooled odds ratios (OR) were appropriately derived from fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy–Weinberg Equilibrium (HWE) was performed. Nine case–control studies on Caucasians (7,304 cases and 8,149 controls) and four case–control studies on Chinese (2,607 cases and 3,022 controls) were eligible. At the overall analysis the A allele seemed to be associated with elevated breast cancer risk; the effect seemed to be confined to homozygous carriers (pooled OR = 1.091, 95% CI: 1.008–1.179, P = 0.030, fixed effects) as heterozygous carriers did not exhibit significantly elevated breast cancer risk. No statistically significant associations were demonstrated in Caucasians. On the other hand, Chinese AA carriers exhibited marginally elevated breast cancer risk (pooled OR = 1.144, 95% CI: 0.984–1.329, P = 0.080, fixed effects). Nevertheless, the controls in two out of the four Chinese studies deviated from HWE. In conclusion, this meta-analysis suggests that the A allele of the CCND1 G870A polymorphism may confer additional breast cancer risk when it comes to homozygosity and Chinese populations. The need for additional, methodologically sound studies on Chinese populations seems warranted.     

Leptin rs2167270 G > A (G19A) polymorphism may decrease the risk of cancer: A case-control study and meta-analysis involving 19 989 subjects

Accumulating evidence has suggested that leptin (LEP) is very important for the development of cancer. Recently, a number of case-control studies about the relationship of the rs2167270 G > A (G19A) variants in the LEP gene with the risk of cancer have yielded inconsistent results. In this study, we have carried out a case-control study [1063 esophagogastric junction adenocarcinoma (EGJA) cases and 1677 controls] in a Chinese population. Furthermore, we carried out a pooled-analysis of 13 studies involving 8059 cancer patients and 11 930 controls to assess whether the LEP G19A locus was associated with overall cancer susceptibility. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were harnessed to evaluate the potential association. In our case-control study, we found an association between the carriers of LEP 19A allele and EGJA risk. In addition, the results of meta-analysis also suggested significant associations with cancer risk (A vs G: OR = 0.92, 95% CI = 0.88–0.97, P = 0.001; AA vs GG: OR = 0.83, 95% CI = 0.74–0.93, P = 0.001, GA/AA vs GG: OR = 0.93, 95% CI = 0.88–0.99, P = 0.023 and AA vs GG/GA: OR = 0.83, 95% CI = 0.74–0.92, P < 0.001). Upon conducting a stratified analysis, we found that LEP 19A allele might decrease the susceptibility of non-Hodgkin lymphoma (NHL) and colorectal cancer (CRC). In a stratified-by-ethnicity analysis, significant associations were also found in Asians, Caucasians, and mixed populations. We can conclude that the LEP G19A polymorphism constitutes a decreased risk of cancer.     

Association between CTLA-4 exon-1 +49A/G polymorphism and systemic lupus erythematosus: an updated analysis

The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to systemic lupus erythematosus are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and SLE, a meta-analysis of 18 published case-control studies was performed. 18 studies meeting our inclusion criteria comprising 1806 SLE cases and 2,490 controls were included. The effect summary odds ratio (OR) and 95 % confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's test and heterogeneity was assessed. The combined results showed that there were significant differences in genotype distribution between SLE cases and control on the basis of all studies, GG versus AA (OR = 1.53, 95 % CI: 1.12-2.10), GG versus GA/AA (OR = 1.30, 95 % CI: 1.04-1.64), GG versus GA (OR = 1.27, 95 % CI: 1.03-1.55). When stratifying for the race, the phenomenon was found that SLE cases had a significantly higher frequency of GG/GA versus AA (OR = 1.58, 95 % CI: 1.23-2.03), GG versus AA (OR = 1.89, 95 % CI: 1.23-2.91), GG versus GA/AA(OR = 1.39, 95 % CI: 1.03-1.89), GA versus AA(OR = 1.38, 95 % CI: 1.06-1.80) and G versus A(OR = 1.34, 95 % CI: 1.07-1.67) than control in Asians. Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for SLE susceptibility, at least in Asians. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of CTLA-4 exon-1 +49A/G polymorphism with SLE susceptibility.     

Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a meta-analysis

IL-27 plays an important role in anti-cancer activity. The -964A/G polymorphism in IL-27 gene has been implicated in susceptibility to cancer, but the results were conflicting. The aim of this study was to assess the association between this polymorphism and cancer risk. Pubmed and Wanfang database were searched for all publications concerning IL-27 -964A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. Statistical analysis was performed using Stata 11.0 software. A total of eight case–control studies including 2044 cancer cases and 2197 controls were identified. Overall, significant association between IL-27 -964A/G polymorphism and cancer risk was observed (GG versus AA: OR?=?1.26, 95% CI?=?1.03–1.52; GG versus AG?+?AA: OR?=?1.20, 95% CI?=?1.00–1.44). In subgroup analysis based on cancer type, significant association was found in colorectal cancer (GG versus AA: OR?=?1.55, 95% CI?=?1.07–2.27; AG versus AA: OR?=?1.31, 95% CI?=?1.02–1.67). The current meta-analysis suggests that IL-27 -964A/G polymorphism might enhance cancer risk. However, large-scale and well-designed studies are still needed to confirm the result of our meta-analysis. The association of IL-27 polymorphism with colorectal cancer may provide insight for future therapies.     

Association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Forty-four reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and lung cancer susceptibility, consisting of 12,363 patients with lung cancer and 13,948 controls. The association between GSTPI G allele and lung cancer risk was found in this meta-analysis (OR 1.08, 95?% CI 1.02–1.15, P?=?0.01). However, the GG genotype and AA genotype were not associated with the susceptibility of lung cancer. Furthermore, there was no association between GSTP1 A/G gene polymorphism and the risk of lung cancer in Caucasians, and East-Asians. In conclusion, GSTP1 G allele is associated with the lung cancer susceptibility. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of lung cancer should be performed in the future.     

Associations between Tumor Necrosis Factor-α Polymorphisms and Risk of Psoriasis: A Meta-Analysis

Background

Tumor necrosis factor-α (TNF-α) may play an important role in the recalcitrant inflammatory and hyperproliferative dermatosis of psoriasis, and there may be a relationship between TNF-α polymorphisms and psoriasis risk.

Methods

We performed a meta-analysis to evaluate the associations between TNF-α polymorphisms and psoriasis. Electronic searches of Pubmed, Embase, and Web of Science were performed for all publications on the associations between TNF-α polymorphisms and psoriasis through September 26, 2012. The pooled odds ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to assess the associations.

Results

Sixteen case-control studies with a total of 2,253 psoriasis cases and 1,947 controls on TNF-α 308 G/A polymorphism and fourteen studies on TNF-α 238 G/A polymorphism with 2,104 cases and 1,838 controls were finally included into the meta-analysis. Overall, TNF-α 308 G/A polymorphism was significantly associated with decreased risk of psoriasis under three genetic comparison models (for A versus G: fixed-effects OR 0.71, 95%CI 0.62-0.82, P < 0.001; for AG versus GG: fixed-effects OR 0.67, 95%CI 0.57-0.78, P < 0.001; for AA/AG versus GG: fixed-effects OR 0.67, 95%CI 0.58-0.78, P < 0.001). In addition, TNF-α 238 G/A polymorphism was associated with increased risk of psoriasis under three genetic models (for A versus G: fixed-effects OR 2.46, 95%CI 2.04-2.96, P < 0.001; for AG versus GG: fixed-effects OR 2.69, 95%CI 2.20-3.28, P < 0.001; for AA/AG versus GG: fixed-effects OR 2.68, 95%CI 2.20-3.26, P < 0.001). Subgroup analysis by ethnicity identified a significant association between TNF-α 308 G/A polymorphism and decreased risk of psoriasis in both Caucasians and Asians and a significant association between TNF-α 238 G/A polymorphism and increased risk of psoriasis in Caucasians.

Conclusions

The meta-analysis suggests that TNF-α 308 G/A polymorphism is associated with decreased risk of psoriasis, while TNF-α 238 G/A is associated with increased risk of psoriasis.     

Glutathione S-transferase P1 gene polymorphism and bladder cancer susceptibility: an updated analysis

Studies investigating the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and bladder cancer (BC) risk have reported conflicting results. In order to clarify the effect of GSTP1 polymorphism on the BC susceptibility, we conducted an updated system review of published epidemiology studies to provide more precise evidence. We performed a systematic search of PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI). 20 studies with 4,428 BC cases and 5,457 controls were identified. The combined analyses based on all studies showed that there was a significant difference in the genotype distribution in GSTP1(A313G) polymorphism between BC cases and controls not only in Asians (GG vs. AA?+?AG, OR?=?1.59, 95?% CI?=?1.01?C2.51) but also in Caucasians (GG vs. AA?+?AG, OR?=?1.51, 95?% CI?=?1.11?C2.06). Upon stratification for smoking status, we observed no statistically significant difference in genotype distribution of GSTP1 in ever-smokers. Combination of the high-risk genotypes (GSTM1 null?+?GSTT1 null?+?GSTP1 313 A/G or G/G) demonstrated further increase in the BC risk (OR?=?6.64, 95?%CI?=?3.63?C12.16). This meta-analysis suggests that GSTP1 313 G/G polymorphism is a strong predisposing risk factor for BC.     

Meta-analysis of MCP-1 promoter ?2518 A/G polymorphism and SLE susceptibility

The aim of this meta-analysis was to summarize results on the association of monocyte chemoattractant protein-1(MCP-1) promoter -2518 A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility. We searches all the publications about the association between MCP-1 promoter -2518 A/G polymorphism and SLE from Pubmed, Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. The meta-analysis was performed for genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG, and A allele verse G allele in a fixed/random effect model. A total of 14 studies (2,333 cases and 2,391 controls) were included in the meta-analysis. When all groups were pooled, we had not observed significant association between A allele and G allele (OR = 0.94, 95 %CI = 0.79-1.12, P = 0.50). When analysis were restricted to more ethnically homogeneous populations, the similar results were found in European population and Asian population (OR = 1.05, 95 %CI = 0.75-1.46, P = 0.80; OR = 1.00, 95 %CI = 0.86-1.17, P = 0.99). However, we had not detected a significant association between MCP-1 promoter -2518 A/G polymorphism and SLE when examining the genotypes AA verse GG, AA+AG verse GG, AA verse AG+GG. The meta-analysis did not demonstrate the association between MCP-1 promoter -2518 A/G polymorphism and SLE.     

HIF-1α 1772 C/T and 1790 G/A Polymorphisms Are Significantly Associated with Higher Cancer Risk: An Updated Meta-Analysis from 34 Case-Control Studies

Background

HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive.

Methodology/Principal Findings

A meta-analysis of 34 studies that involved 7522 cases and 9847 controls for 1772 C/T and 24 studies that involved 4884 cases and 8154 controls for 1790 G/A was conducted to identify the association of C/T and G/A polymorphisms with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association.HIF-1α 1772 C/T and 1790 G/A polymorphisms were associated with higher cancer risk in homozygote comparison (1772C/T: TT vs. CC: OR = 2.45, 95% CI: 1.52, 3.96; P _{heterogeneity} = 0.028; 1790G/A: AA vs. GG: OR=4.74, 95% CI: 1.78, 12.6; P _{heterogeneity} < 0.01), dominant model (1772C/T: TT/CT vs. CC: OR = 1.27, 95% CI: 1.04, 1.55; P _{heterogeneity} < 0.01, 1790G/A: AA/GA vs. GG: OR = 1.65, 95% CI: 1.05, 2.60; P _{heterogeneity} < 0.01), T allele versus C allele (T vs. C: OR = 1.42, 95% CI: 1.18, 1.70; P _{heterogeneity} < 0.01), and A allele versus G allele (A vs. G: OR = 1.83, 95% CI: 1.13, 2.96; P _{heterogeneity} < 0.01). On a subgroup analysis, the 1772 C/T polymorphism was significantly linked to higher risks for breast cancer, lung cancer, prostate cancer, and cervical cancer, whereas the 1790 G/A polymorphism was significantly linked to higher risks for lung cancer and prostate cancer. A significantly increased cancer risk was found in both Asians and Caucasians for 1772C/T polymorphism, whereas a significantly increased cancer risk was found in Caucasians in the heterozygote comparison and recessive model for 1790G/A polymorphism.

Conclusions

HIF-1α 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk.     

Quantitative assessment of the association between TAP2 rs241447 polymorphism and cancer risk

The findings regarding the relation of transporter associated with antigen processing (TAP) to cancer risk have been inconsistent. The aim of this study was to comprehensively evaluate the association between TAP2 rs241447 polymorphism and cancer susceptibility. A meta-analysis of nine investigations with 2800 cases and 1620 controls was conducted to gain a better understanding of the effect of TAP2 rs241447 polymorphism on cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the correlation between TAP2 gene polymorphism and cancer susceptibility. The pooled results from TAP2 rs241447 polymorphism showed a decreased risk of cancer in two dominant genetic models (GG + AG vs AA: OR = 0.86, 95% CI, 0.75-0.99; AG vs AA: OR = 0.85, 95% CI, 0.73-0.99). From the subgroup analysis, decreased cancer susceptibility was found in Caucasians (GG + AG vs AA: OR = 0.82, 95% CI, 0.68-0.99), especially among the subgroup of cervical carcinoma (GG + AG vs AA: OR = 0.82, 95% CI, 0.69-0.96; AG vs AA: OR = 0.83, 95% CI, 0.70-0.99). Overall, the results suggest that TAP2 rs241447 polymorphism contributes to decreased cancer susceptibility.     

Cyclin D1 G870A polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case–control study

Background: A common G to A polymorphism (G870A) in the splice donor region of exon 4 of cyclin D1 (CCND1) gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of this polymorphism. Cyclin D1a and b proteins differ in their COOH-terminus, a region involved in protein degradation. We examined the association between this CCDN1 genotype and the susceptibility to hepatocellular carcinoma (HCC) in a Turkish population. Methods: The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Hospital-based case–control study was designed consisting of 160 diagnosis subjects with hepatocellular carcinoma and 160 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: The allele frequencies of case subjects (A, 0.55; G, 0.45) were significantly different from those of control subjects (A, 0.42; G, 0.58) (p = 0.002). The odds ratios (ORs) for the CCND1 870 GA and AA genotypes when compared with the GG genotypes were 1.39 (95% confidence interval [CI] 0.82–2.36, p = 0.22) and 2.52 (95% CI 1.38–4.62, p = 0.003) respectively. The presence of at least one CCND1 870A allele was associated with increased risk for HCC (OR, 1.73; 95% CI, 1.06–2.82, p = 0.03). When combining the GG and GA genotypes as a reference genotype, we found that the OR for the AA genotype was 2.06 (95% CI 1.24–3.44, p = 0.006). Conclusion: Our results suggest that the CCND1 G870A single nucleotide polymorphism is associated with an increased risk of HCC in our Turkish population.     

Meta-analysis of epidermal growth factor polymorphisms and cancer risk: involving 9,779 cases and 15,932 controls

The epidermal growth factor (EGF) pathway stimulates proliferation and differentiation of epidermal and epithelial tissues, and plays an important role in tumorigenesis. The association between EGF polymorphisms and cancer risk is controversial; thus, we performed this meta-analysis. Overall, 41 case-control studies with 9,779 cases and 15,932 controls were retrieved. We found that EGF +61A/G polymorphism increased overall cancer risk (G allele vs. A allele: OR=1.181, 95% CI=1.077-1.295, P(heterogeneity) < 0.001; GG vs. AA: OR=1.370, 95% CI=1.143-1.641, P(heterogeneity) < 0.001; GG+GA vs. AA: OR=1.175, 95% CI=1.047-1.318, P(heterogeneity) < 0.001). In the stratified analysis by cancer type, the +61?G allele was a risk factor for colorectal cancer, esophageal carcinoma, gastric cancer, and hepatocellular carcinoma. Individuals who carried +61G allele had higher cancer susceptibility in mixed and European racial subgroups. An increased association was detected in the hospital-based subgroup. No significant association was found among EGF -1380A/G, -1744G/A, rs6983267T/G polymorphisms and cancer risk.     

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.     

The E-cadherin (CDH1) -C160A polymorphism and colorectal cancer susceptibility: a meta-analysis

E-cadherin, encoded by the CDH1 gene, involves in invasion and metastasis of cancer cells. CDH1 -C160A polymorphism was shown to contribute to genetic susceptibility to colorectal cancer (CRC). However, the results from different studies remain controversial. This study was conducted to further explore the association between CDH1 -C160A genetic polymorphism and CRC susceptibility by means of a meta-analysis. A comprehensive literature search was conducted to identify all case-control studies of CDH1 -C160A polymorphism and risk for CRC. A total of nine eligible studies, including 7954 CRC cases and 7369 controls, were identified to the meta-analysis. On the whole, the meta-analysis indicated that CDH1 -C160A genetic polymorphism could reduce the risk of CRC under AA versus CC contrast (odds ratio [OR]=0.86, 95% confidence interval [CI]=0.75-0.98, p(heterogeneity)=0.11), recessive model (OR=0.88, 95% CI=0.77-0.99, p(heterogeneity)=0.23), dominant model (OR=0.92, 95% CI=0.87-0.99, p(heterogeneity)=0.11), and allele A versus allele C contrast (OR=0.93, 95% CI=0.88-0.98, p(heterogeneity)=0.26). A conclusion could be drawn from the research that CDH1 -C160A polymorphism provides a possible protection against CRC, which is especially evident in Caucasian and hospital populations.