Studies investigating the relationship between TP53 Arg72Pro polymorphism and endometrial cancer risk reported conflicting results. To explore a more precise estimate of the effect of this polymorphism on endometrial carcinogenesis, a meta-analysis was performed by searching eligible studies in PubMed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association for codominant model (Arg/Arg vs. Pro/Pro, Arg/Pro vs. Pro/Pro), dominant model (Arg/Arg+Arg/Pro vs. Pro/Pro), and recessive model (Arg/Arg vs. Arg/Pro+Pro/Pro), respectively. Subgroup analyses were performed by Hardy-Weinberg equilibrium (HWE) in controls, the specimen of cases for determining TP53 genotypes, sample size, the source of control and case groups, and ethnicity. We identified 8 case-control studies involving 2,154 subjects for this meta-analysis. Overall, no evidence of association was observed between TP53 genotypes and endometrial cancer risk in all genetic models (Arg/Arg vs. Pro/Pro: OR=0.98, 95% CI: 0.69-1.39, P=0.90; Arg/Pro vs. Pro/Pro: OR=1.00, 95% CI: 0.71-1.42, P=0.98; dominant model: OR=0.99, 95% CI: 0.71-1.38, P=0.95; recessive model: OR=1.06, 95% CI: 0.80-1.41, P=0.95). Stratified analyses also detected no significant association in any subgroup, except among those studies with controls deviated from HWE in recessive model (OR=1.60, 95% CI: 1.07-2.39). In conclusion, we did not observe any evidence for a role of TP53 Arg72Pro polymorphism in endometrial cancer. The reported significant association between this polymorphism and endometrial cancer risk may be due to methodological errors such as selection bias, small sample size, Type I error, and population stratification.

The X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) gene is a member of the RAD51 gene family. It encodes an important protein that functions in the homologous recombination repair of DNA double-strand break. In this study, our aim was to explore the relationship between XRCC3 T241M polymorphism and gastric cancer risk. Performing both the overall meta-analysis and subgroup meta-analysis based on ethnicity, source of controls, and cancer location with a total of 6 eligible studies (1,154 cases and 1,487 controls in all), we detected no significant gastric cancer risk variation for all genetic models in the overall analysis and in the subgroup analysis based on cancer location. What is interesting is in the subgroup analysis based on ethnicity, where significantly decreased gastric cancer risk was observed for recessive model in Asians (OR=0.69, 95% CI=0.50-0.95), while significantly increased gastric cancer risk was detected for dominant model in Caucasians (OR=1.45, 95% CI=1.01-2.08). In summary, according to the results of our meta-analysis, the XRCC3 T241M polymorphism might influence gastric cancer risk oppositely in Asians and Caucasians.

Recent genome-wide association studies (GWAS) identified genetic loci associated with pigmentation, nevi, and skin cancer. We performed a review and meta-analysis of GWAS results, grouping them into four categories: (i) loci associated with pigmentation (hair, eye, and/or skin color), cutaneous UV-response (sun sensitivity and/or freckling), and skin cancer; (ii) loci associated with nevi and melanoma; (iii) loci associated with pigmentation and/or cutaneous UV-response but not skin cancer; and (iv) loci associated distinctly with skin cancer, mostly basal cell carcinoma, but not pigmentation or cutaneous UV-response. These findings suggest at least two pathways for melanoma development (via pigmentation and via nevi), and two pathways for basal cell carcinoma development (via pigmentation and independent of pigmentation). However, further work is necessary to separate the association with skin cancer from the association with pigmentation. As with any GWAS, the identified loci may not include the causal variants and may need confirmation by direct genome sequencing.

Epidemiological studies have evaluated the association between ATM C.1066-6T > G (IVS10-6T > G) mutation and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of 11 studies including 8,831 cases and 4,957 controls were identified. The carrier frequency of the ATM C.1066-6T > G mutation was 0.5% (45/8,831) in patients with breast cancer and 0.7% (38/4,957) in healthy controls. When all the 11 studies were pooled into the meta-analysis, there was no evidence for significant association between C.1066-6T > G mutation and breast cancer risk (OR 0.87, 95% CI 0.55-1.37). In the subgroup analyses by source of controls and family history with BRCA1/2 status, no significant association were found in any subgroup of population. When sensitivity analyses were performed, all the results were not materially altered. In summary, the meta-analysis strongly suggests that ATM C.1066-6T > G mutation is not associated with increased breast cancer risk.

Genetic variations in metabolic genes are considered to modulate metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we evaluated reported studies of association between polymorphism of glutathione S-transferase T1 gene (GSTT1) and the risk of lung cancer in Chinese population. We found an increased lung cancer risk among subjects carrying GSTT1 null genotype [odds ratio (OR)=1.36, 95 percent confidence interval (95% CI): 1.09-1.69], using 1625 cases and 2188 controls from 11 studies. We also observed an increased risk of lung cancer among null genotype carriers in squamous cell carcinoma and adenocarcinoma, and on the basis of population control in stratified analyses. The meta-analysis suggests that GSTT1 deletion polymorphisms may have an effect on the susceptibility of lung cancer in Chinese population, and a study with the larger sample size is needed to further evaluate gene-gene and gene-environment interaction on GSTT1 deletion polymorphisms and lung cancer risk in Chinese population.

Women with BRCA1 or BRCA2 mutations are at increased risk of breast and ovarian cancer. Oral contraceptives (OC) use has been associated with a reduction in ovarian cancer risk and with a moderately increased breast cancer risk, which tends to level off in the few years after stopping. The association between oral contraceptive and BRCA1 or BRCA2 gene mutations carriers is unclear.

Desmoid tumours (DT) are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP). Several small series have analysed the incidence of DT and predisposing risk factors. Using meta-analytical techniques, this study aimed to identify risk factors for DT development in patients with FAP.

Several molecular epidemiological studies were conducted in recent years to evaluate the association between NQO1 Pro187Ser polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 3177 cases with breast cancer and 4038 controls from seven published case-control studies showed that the 187Ser allele was not associated with a significantly increased risk of breast cancer (Ser versus Pro: P = 0.33, OR = 1.08, 95% CI = 0.92-1.28; Ser/Ser versus Pro/Pro: P = 0.58, OR = 1.16, 95% CI = 0.68-2.00; Ser/Ser versus Pro/Ser + Pro/Pro: P = 0.62, OR = 1.14, 95% CI = 0.68-1.90; Ser/Ser + Pro/Ser versus Pro/Pro: P = 0.30, OR = 1.07, 95% CI = 0.94-1.22). In the stratified analysis by ethnicity, we found that the Pro187Ser polymorphism was associated with increased breast cancer risk in Caucasians in the additive genetic model and dominant genetic model (P = 0.03, OR = 1.13, 95% CI = 1.01-1.26; P = 0.03, OR = 1.15, 95% CI = 1.01-1.30, respectively), whereas no significant in Asians (P = 0.44, OR = 0.94, 95% CI = 0.80-1.10) and postmenopausal women (P = 0.99, OR = 1.00, 95% CI = 0.84-1.19). The results suggest that NQO1 Pro187Ser polymorphism may contribute to breast cancer development in Caucasians.

Glutathione S-transferase P1 (GSTP1) is involved in a wide range of detoxifying reactions. Any alteration in the structure, function, or expression of GSTP1 gene may alter the ability of a cell to inactivate carcinogens or mutagens, and thus modify an individual's risk to cancer. Previous epidemiological studies on the potential association between GSTP1 Ile105Val polymorphism and breast cancer risk have produced inconsistent results. In order to drive a more precise estimation of this association, we performed a meta-analysis of 30 published case-control studies including 15,901 cases and 18,757 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The results of this meta-analysis showed that GSTP1 Ile105Val polymorphism was not associated with breast cancer susceptibility in overall population. However, in subgroup analysis by ethnicity, we found a significant association among Asian population (for Val/Val vs. Ile/Ile: OR 1.27, 95% CI 1.02-1.83; for the recessive model Val/Val vs. Ile/Ile + Ile/Val: OR 1.42, 95% CI 1.20-1.69). When stratified by study design, significantly elevated susceptibility to breast cancer was found among hospital-based studies (for Val/Val vs. Ile/Ile: OR 1.38, 95% CI 1.16-1.63; for recessive model Val/Val vs. Ile/Val + Ile/Ile: OR 1.31, 95% CI 1.12-1.55; for dominant model: Val/Val + Ile/Val vs. Ile/Ile: OR 1.10, 95% CI 1.02-1.19). In conclusion, our meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase susceptibility to breast cancer in Asian population.

Epidemiological studies have investigated the association between HER2 codon 655 polymorphism and breast cancer susceptibility. However, the results are still inconclusive. To obtain a more precise estimation of the relationship, this meta-analysis was performed. A total of 22 studies including 9,209 cases and 10,132 controls were collected. The strength of association between HER2 codon 655 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 22 studies were pooled into the meta-analysis, there was no evidence for significant association between HER2 codon 655 polymorphism and breast cancer susceptibility (for Val/Ile vs. Ile/Ile: OR = 1.069, 95% CI = 0.976-1.172; for Val/Val vs. Ile/Ile: OR = 1.191, 95% CI = 0.922-1.538; for dominant model: OR = 1.093, 95% CI = 0.991-1.206; for recessive model: OR = 1.141, 95% CI = 0.902-1.444). In the subgroup analysis by the source of controls and ethnicity, no significant increased risk was found in all genetic models. However, the current results indicated the modest association between the HER2 Ile655Val polymorphism and Asian population (Val/Ile vs. Ile/Ile: OR = 1.207, CI = 1.006-1.450). In summary, the meta-analysis suggests that HER2 codon 655 polymorphism is not associated with the increased breast cancer risk.

To evaluate the contribution of candidate gene association studies to the understanding of genetic susceptibility to childhood acute lymphoblastic leukemia we conducted a systematic review and meta-analysis of published studies (January 1996-July 2009). Studies had to meet the following criteria: be case-control design, be studied by two or more studies, not be focused on HLA antigen genetic markers and be published in English. We identified 47 studies of polymorphic variation in 16 genes and acute lymphoblastic leukemia risk. To clarify the impact of individual polymorphisms on risk, pooled analyses were performed. Of the 25 polymorphic variants studied, significant associations (P<0.05) were seen in pooled analyses for eight variants: GSTM1 (OR =1.16; 95%CI: 1.04-1.30), MTRR A66G (OR=0.73, 95%CI:0.59-0.91), SHMT1 C1420T (OR=0.79, 95%CI: 0.65-0.98), RFC1 G80A (OR=1.37, 95%CI: 1.11-1.69), CYP1A1*2A (OR=1.36, 95%CI:1.11-1.66), CYP2E1*5B (OR=1.99, 95%CI:1.32-3.00) NQO1 C609T (OR=1.24, 95%CI:1.02-1.50) and XRCC1 G28152A (OR=1.78, 95%CI:1.32-2.42). These findings should, however, be interpreted with caution as the estimated false-positive report probabilities (FPRP) for each association were not noteworthy (i.e. FPRP>0.2). While candidate gene analyses are complementary to genome-wide association studies, future analyses should be based on sample sizes commensurate with the detection of small effects and attention needs to be paid to study design.

Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1 codon 213 polymorphism by searching the databases of Medline, PubMed, Embase, and ISI Web of Knowledge. The strength of association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 21 studies were pooled into the meta-analysis, there was no evidence for significant association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility (for Arg/Arg versus Arg/His: OR = 0.999, 95% CI = 0.941-1.061; for Arg/Arg versus His/His: OR = 1.121, 95% CI = 1.013-1.242; for dominant model: OR = 1.128, 95% CI = 1.01-1.26; for recessive model: OR = 1.151, 95% CI = 0.950-1.394). In the subgroup analysis by the source of controls, significant increased risk was found for hospital-based studies (for Arg/Arg versus Arg/His: OR = 1.173, 95% CI = 1.000-1.376; for Arg/Arg versus His/His: OR = 1.600, 95% CI = 1.134-2.256; for dominant model: OR = 1.269, 95% CI = 1.134-2.256; for recessive model: OR = 1.664, 95% CI = 1.070-2.588). In summary, the meta-analysis suggests that SULT1A1 codon 213 polymorphism may be associated with the hospital-based studies. However, large number of samples and representative hospital-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

The murine double minute 2 (MDM2) gene encodes an important regulator which mainly functions as an E3 ligase. The role of the MDM2 protein in the P53 pathway has been especially well-studied. In this study, our aim was to explore the relationship between MDM2 gene 309 T/G polymorphism and colorectal cancer risk. Performing both the overall meta-analysis and the subgroup meta-analysis based on ethnicity and source of controls with a total of 7 eligible studies (2,543 cases and 2,115 controls in all), we detected a significant colorectal cancer risk variation for TG versus GG (OR=0.73, 95% CI=0.62-0.86) in the overall analysis and another significant colorectal cancer risk variation for TG versus GG (OR=0.70, 95% CI=0.59-0.83) in the population-based controls' subgroup as well. Moreover, in the subgroup analysis based on ethnicity, significant associations were observed for all genetic models in Asians (OR=0.51, 95% CI=0.41-0.64 for TT versus GG; OR=0.64, 95% CI=0.53-0.78 for TG versus GG; OR=0.59, 95% CI=0.49-0.71 for dominant model; OR=0.69, 95% CI=0.57-0.82 for recessive model), while in Caucasians there was no obvious association. In summary, according to the results of our meta-analysis, the MDM2 309 G allele probably acts as a colorectal cancer risk factor, especially in Asians.

Several studies have investigated the associations between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and the susceptibility to lung cancer and bladder cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 22 case control studies, including 2976 cases and 4495 controls for lung cancer, and 3445 cases and 4599 controls for bladder cancer, met the inclusion criteria and were selected. Overall, there was no evidence showing a significant association between XRCC3 Thr241Met polymorphism and lung cancer risk. Furthermore, the results for bladder cancer showed that significant decreased risk was found for the additive model (odds ratio [OR] = 0.959, 95% confidence interval [CI], 0.924-0.996) and dominant model (OR = 0.982, 95% CI, 0.963-1.000) but not for the recessive model (OR = 0.958, 95% CI, 0.905-1.014). In summary, our meta-analysis indicates that XRCC3 Thr241Met polymorphism may be weakly associated with the risk of bladder cancer. (Cancer Sci 2010).

Conflicting data have been published as to the possible association between polymorphism in codon 72 of the TP53 tumor suppressor gene and the risk of developing breast cancer. In order to address this question, we carried out a meta-analysis of 21 studies of and this polymorphism and breast cancer risk, which collectively included 12,601 cases and 11,462 controls. Studies were identified by searching the Medline, PubMed, Embase, and ISI Web of Knowledge databases. The strength of association between the TP53 codon 72 polymorphism and breast cancer risk was assessed by calculating crude OR values with 95% CIs, with pooled OR values calculated separately for three genetic inheritance models. We found no significant association between TP53 codon 72 polymorphism and breast cancer risk for either the codominant inheritance model (Pro/Arg vs. Pro/Pro: OR = 1.063, 95% CI = 0.967-1.169; Arg/Arg vs. Pro/Pro: OR = 1.245, 95% CI = 0.997-1.554), the dominant model (OR = 1.146, 95% CI = 0.979-1.340), or the recessive model (OR = 1.179, 95% CI = 1.020-1.362). Stratified analysis by ethnicity and source of controls similarly revealed no significant association for any of the genetic models. In summary, this meta-analysis provides strong evidence that the TP53 codon 72 polymorphism is not associated with the risk of developing breast cancer.

Cyclin D1 (CCND1) is a key regulatory protein in the G1/S checkpoint of the cell cycle. We hypothesized that the G870A polymorphism of CCND1 is associated with the risk for cervical cancer and performed a meta-analysis of eligible studies to evaluate this relationship.

Case/control studies that investigated the association between gastric cancer and the MTHFR C677T and A1298C polymorphisms so far have provided controversial results. To clarify the effect of MTHFR polymorphisms on the risk of gastric cancer, a meta-analysis was performed.

Epidemiological studies have evaluated the association between catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 41 studies including 25,627 cases and 34,222 controls were identified. Genotype distributions of COMT in the controls of all studies were in agreement with the Hardy-Weinberg equilibrium (HWE) except for three studies. When all 41 studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val108/158Met polymorphism and breast cancer risk (for Val/Met vs. Val/Val: OR = 0.99, 95% CI = 0.93-1.04; for Met/Met vs. Val/Val: OR = 0.96, 95% CI = 0.88-1.04; for dominant model: OR = 0.97, 95% CI = 0.92-1.03; for recessive model: OR = 0.97, 95% CI = 0.90-1.04). In the subgroup analyses by ethnicity, menopausal status, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that COMT Val108/158Met polymorphism is not associated with increased breast cancer risk.

Several studies have investigated the associations between AURKA T91A polymorphism and the susceptibility to breast cancer, but the results have been inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 11 case-control studies, including 14,361 cases and 17,780 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, and recessive model. When all the studies were pooled into the meta-analysis, there was no evidence showing a significant association between AURKA T91A polymorphism and breast cancer risk (for additive model, OR = 0.839, 95% CI = 0.678-1.038; for dominant model: OR = 0.890, 95% CI = 0.757-1.074; and for recessive model: OR = 0.987, 95% CI = 0.963-1.012). In the subgroup analysis by ethnicity, significantly decreased risks were found for Asians (additive model, OR = 0.857, 95% CI = 0.742-0.991). When stratified by study design, no significant association was found between the polymorphism and breast cancer risk. In conclusion, this meta-analysis indicates that the AURKA T91A polymorphism is not a risk factor for developing breast cancer.

A single-nucleotide polymorphism (SNP) in the 5'-untranslated region (UTR) of RAD51, 135G>C (rs1801320), was reported to be associated with an increased risk of breast cancer among BRCA2 as well as BRCA1 carriers. A few studies have also investigated the genetic contribution of RAD51 135G>C to the risk of sporadic breast cancers or breast cancer in non-BRCA1/2 carriers, though the results are yet controversial and inconclusive. We, in this study, performed a more precise estimation of the relationship between 135G>C and breast cancer among non-BRCA1/2 mutation carriers by meta-analyzing the currently available evidence from the literature. A total of 12 studies involving 7,065 cases and 6,981 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, there was no evidence for a significant association between 135G>C and breast cancer risk in non-BRCA1/2 mutation carriers (for CC vs. GG: OR = 0.995, 95%CI: 0.741-1.336; for GC vs. GG: OR = 0.959, 95%CI: 0.869-1.057; for dominant model: OR = 0.988, 95%CI: 0.902-1.082; and for recessive model: OR = 1.037, 95%CI: 0.782-1.376). We also performed subgroup analysis by ethnicity (Caucasian) as well as did analysis using the studies fulfilling Hardy-Weinberg equilibrium, and the results did not change. In summary, the present meta-analysis suggests that the RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers.