To date, many publications discussed the correlation between ERCC2 Asp312Asn polymorphism and breast cancer risk. However, the results were not unanimous. In order to derive a more precise conclusion, a meta-analysis was performed in this study by searching Medline, PubMed, and ISI Web of Knowledge databases. Finally, 17 studies including 12,019 cases and 10,747 controls were collected for this meta-analysis. The strength of association between ERCC2 Asp312Asn polymorphism and breast cancer risk was assessed by calculating crude ORs with 95% CIs. Overall, no significant associations between ERCC2 Asp312Asn polymorphism and breast cancer susceptibility were found. In the stratified analysis by ethnicity, significant associations were observed for Asn/Asn versus Asp/Asp (OR = 0.55; 95% CI 0.32-0.96) and Asn/Asn versus Asn/Asp + Asp/Asp (OR = 0.53; 95% CI 0.32-0.90) in Asians. In the stratified analysis by study design, significant associations were found for Asn/Asn versus Asp/Asp (OR = 0.79; 95% CI 0.64-0.98) and Asn/Asn versus Asn/Asp + Asp/Asp (OR = 0.82; 95% CI 0.68-0.99) in population-based studies. In conclusion, this meta-analysis provides an evidence that ERCC2 312Asn allele may have a protective effect for breast cancer development in Asians.

The Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) project aims to additionally explore the data of the two large, randomized, cooperative-group studies comparing two doses of imatinib (400 mg daily v twice daily) in 1,640 patients with advanced GIST.

Sporadic colorectal cancer (CRC) is considered to be a multifactorial disease, in which multiple exposures to endogenous factors interact with individual genetic background in a complex manner, resulting in modulation of the risk. The glutathione S-transferase M1 gene (GSTM1) is a particularly attractive candidate for CRC susceptibility because it codes an enzyme involved in the metabolism of environmental carcinogens. However, the epidemiological findings have been inconsistent.

Studies on polymorphisms of Xeroderma Pigmentosum Group D Protein (XPD) and breast cancer risk are inconclusive. To elucidate the role of XPD genotypes, all available studies were considered in this meta-analysis. The study provided 11,362/10,622 cases/controls for XPD K751Q and 9010/9873 cases/controls for XPD D312N, respectively. Overall, no apparent effects of 751Q allele compared to 751K on breast cancer risk was found in all subjects [RE OR = 1.04, 95% confidence interval (CI) (0.97-1.10), P = 0.28]. Insignificant effects were also found under other genetic contrasts (homologous contrast, dominant model, and recessive model). However, the 751Q allele showed significantly increased risk in Caucasians [FE OR = 1.05, 95% CI (1.00-1.11), P = 0.035]. In addition, insignificant risk effects of D312N polymorphism on breast cancer susceptibility were observed in all subjects under any genetic contrast, but protective effects of 312NN genotype were observed under recessive model [P = 0.02, OR = 0.53, 95% CI (0.32, 0.90)] and homozygote contrast [P = 0.03, OR = 0.55; 95% CI (0.32, 0.96)] in Asians. In summary, our meta-analysis suggested 312N allele might act as a recessive allele in its association with breast cancer and the 751Q allele may play a plausible role in breast cancer development whereas the ethnic background should be carefully concerned in further studies.

The A2756G polymorphism in the methionine synthase (MTR) gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case-control studies, including 8,438 breast cancer cases and 10,515 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, no significant associations between the MTR A2756G polymorphism and breast cancer risk were found for GG versus AA (OR = 0.98, 95% CI: 0.84-1.15), AG versus AA (OR = 0.95, 95% CI: 0.89-1.01), GG/AG versus AA (OR = 0.95, 95% CI = 0.89-1.01), and GG versus AG/AA (OR = 1.00, 95% CI: 0.86-1.17). However, in the stratified analysis, significantly decreased breast cancer risks were found among Europeans (AG versus AA, OR = 0.90, 95% CI = 0.83-0.98; GG/AG versus AA, OR = 0.90, 95% CI = 0.82-0.97) and studies with population-based controls (AG versus AA, OR = 0.93, 95% CI = 0.86-1.00; GG/AG versus AA, OR = 0.93, 95% CI = 0.86-1.00). When stratifying by the menopausal status, no significant result was observed in all genetic models. Taken together, the results suggest that the MTR A2756G polymorphism may contribute to susceptibility to breast cancer among Europeans.

The fms-like tyrosine kinase 3 (FLT3) gene aberrations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations, are frequent in acute promyelocytic leukemia (APL). To evaluate their prognostic significance, we performed a systematic review and meta-analysis. Eleven studies covering a total of 1063 subjects were included in this review. Incidence of ITD and TKD mutations was 12-38% and 2-20%, respectively. In 9 of 11 studies, ITD was associated with high WBC count at the time of diagnosis, which is a known prognostic indicator in APL. Patients with ITD had inferior 3-year overall survival compared to patients without ITD (risk ratio 1.42, 95% CI: 1.04-1.95). Similarly, ITD was also associated with adverse 3-year disease-free survival (risk ratio 1.48, 95% CI: 1.02-2.15). There were only two studies that evaluated the association of TKD mutation in APL; both showed a trend towards worse survival in patients with mutated TKD. In conclusion, FLT3 ITD is associated with high WBC at diagnosis in patients with APL. Although the available literature is limited to observational studies, our systematic review suggests that FLT3 mutations, especially ITD, can adversely affect overall survival and disease-free survival in APL.

A few genetic polymorphisms of TP53 are known to have a significant effect on cancer susceptibility. Intron 3 16 bp duplication polymorphism of TP53 has been reported to be associated with breast cancer, colorectal cancer, lung cancer and other cancers, but the reported results remain inconclusive. The present study, a meta-analysis including a total of 9801 cases and 10,391 controls from 26 studies, revealed that the 16 bp insertion (Ins) allele is significantly associated with an increased cancer risk in overall analysis [Ins/Ins + deletion (Del)/Ins versus Del/Del: odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.02-1.27, P = 0.02; Ins/Ins versus Del/Del: OR = 1.35, 95% CI = 1.11-1.63, P = 0.002; Del/Ins versus Del/Del: OR = 1.10, 95% CI = 0.98-1.23, P = 0.11.), particularly in breast cancer subgroup (Ins/Ins + Del/Ins versus Del/Del: OR = 1.16, 95% CI = 1.03-1.31, P = 0.02; Ins/Ins versus Del/Del: OR = 1.81, 95% CI = 1.30-2.52, P < 0.001; Del/Ins versus Del/Del: OR = 1.10, 95% CI = 0.97-1.25, P = 0.13). The relative risks to the colorectal and lung cancers increased but their association power was relatively weak, which may result from a limited number of studies of these two cancer types. These results suggest that intron 3 16 bp duplication polymorphism of TP53 is potentially an important and clinically relevant genetic marker contributing to cancer susceptibility.

Relationship of gastric cancer with the presence of IL-10-592 polymorphism was reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between IL-10-592 allele polymorphism and gastric cancer susceptibility. We performed an extensive search of relevant studies and made a meta-analysis, including 12 studies with 2,285 gastric cancer cases and 4,236 controls. The combined results based on all studies showed that there were no significant differences in genotype distribution between gastric cancer cases and controls, CC versus CA/AA (OR = 1.05, 95% CI: 0.92-1.18), CC/CA versus AA (OR = 1.16, 95% CI: 0.92-1.46), CC versus CA (OR = 1.03, 95% CI: 0.90-1.17), CC versus AA (OR = 1.10, 95% CI: 0.90-1.34), and CA versus AA (OR = 1.16, 95% CI: 0.92-1.45). When stratifying for the race, it was found that gastric cancer cases had a significantly higher frequency of CC/CA versus AA (OR = 1.31, 95% CI: (1.08-1.59) and a significantly upper frequency of CA versus AA (OR = 1.33, 95% CI: 1.09-1.63) than control in Asians. When stratifying for the location and the Lauren's classification of gastric cancer, there were no statistically significant differences in genotype distribution between gastric cancer cases and controls. This meta-analysis suggested that IL-10-592 allele polymorphism might be a risk factor for gastric cancer among Asians.

Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) plays an important role in breast cancer development. To date, many publications have evaluated the correlation between UGT1A1 TA-repeat polymorphism and breast cancer risk. However, the results remain inconclusive. In order to resolve this conflict, a meta-analysis was performed by searching Medline, PubMed, and ISI Web of Knowledge databases. Seven studies including 5,746 cases and 8,365 controls were collected for UGT1A1 TA-repeat polymorphism. The strength of association between UGT1A1 TA-repeat polymorphism and breast cancer risk was assessed by calculating crude ORs with 95% CIs. Overall, no significant associations between UGT1A1 TA-repeat polymorphism and breast cancer susceptibility were found. In the stratified analysis by ethnicity and source of controls, significant associations were only observed for 6/6 versus 7/7 (OR = 0.88; 95% CI: 0.77-0.99; P = 0.425 for heterogeneity) in Caucasians, but no in other genetic models. In conclusion, this meta-analysis suggests that UGT1A1 A(TA)(7)TAA allele is a potential risk factor for breast cancer in Caucasians.

There is a need to develop robust and clinically applicable gene expression signatures. Hypoxia is a key factor promoting solid tumour progression and resistance to therapy; a hypoxia signature has the potential to be not only prognostic but also to predict benefit from particular interventions.

Published data on the association between insulin-like growth factor binding protein 3 (IGFBP3) A-202C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 27 studies including 33,557 cases and 45,254 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with IGFBP3 C allele when all studies were pooled into the meta-analysis (CC vs. AA: OR = 1.06, 95% CI = 1.02-1.11; dominant model: OR = 1.04, 95% CI = 1.00-1.07). In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (AC vs. AA: OR = 1.04, 95% CI = 1.00-1.08; CC vs. AA: OR = 1.05, 95% CI = 1.01-1.10; dominant model: OR = 1.04, 95% CI = 1.00-1.08) and Asians (CC vs. AA: OR = 1.35, 95% CI = 1.02-1.78; recessive model: OR = 1.38, 95% CI = 1.05-1.82). When stratified by study design, statistically significantly elevated risk was found among population-based studies (CC vs. AA: OR = 1.06, 95% CI = 1.01-1.11; dominant model: OR = 1.03, 95% CI = 1.00-1.07). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. In conclusion, this meta-analysis suggests that the IGFBP3 C allele is a low-penetrant risk factor for developing breast cancer.

Previous published data have implicated TP53 codon 72 polymorphisms as risk factors for various cancers. Growing bodies of studies have been conducted on the association of TP53 codon 72 polymorphisms with susceptibility to oral carcinoma and have yielded inconclusive results. The aim of the present study was to derive a more precise estimation of this relationship.

Published studies on the association between the progesterone receptor gene +331 G/A polymorphism and breast cancer risk are inconclusive, and meta-analysis is required to verify the association. Six studies, including a total of 6,849 cases and 6,589 controls, were subjected to meta-analysis. When all eligible subjects were pooled for meta-analysis, the AG + AA variant genotype was not associated with a significantly elevated breast cancer risk [odds ratio (OR) = 1.11; 95% confidence interval (95%CI) = 0.99-1.24; P = 0.071]. However, subgroup analysis revealed that the AG + AA variant genotype was associated with an increased risk of breast cancer in American (OR = 1.32; 95%CI = 1.10-1.58; P = 0.003), but not in European or Australian. We could carefully suggest that the progesterone receptor promoter +331 G/A variant polymorphism might increase breast cancer risk, and this effect appeared to be more prominent in Americans than in Europeans and Australians.

Sex steroid hormones and their receptors such as estrogen receptor (ER) and progesterone receptor (PgR) have been widely studied for their roles in the etiology of breast cancer. To date, many studies have evaluated the association between a functional polymorphism in the PgR gene promoter (+331G>A, rs10895068) and breast cancer risk; however, the result is still ambiguous and inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. By searching relevant literature, a total of 10 studies containing 13,702 cases and 14,726 controls (28,428 subjects in total) were identified and meta-analyzed. All the study subjects were Caucasian women. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, dominant model, and recessive model. Overall, no significant association between +331G>A polymorphism and breast cancer susceptibility was observed for AA versus GG (OR = 0.940, 95% CI: 0.566-1.562), GA versus GG (OR = 1.061, 95% CI: 0.888-1.267), AA + GA versus GG (OR = 1.074, 95% CI: 0.956-1.207), and AA versus GA + GG (OR = 0.951, 95% CI: 0.586-1.544). Sensitivity analysis was performed by limiting the meta-analysis to those studies fulfilling Hardy-Weinberg equilibrium, and the results were not materially altered in any genetic model. In conclusion, the present meta-analysis strongly suggests that +331G>A in the PgR gene is not associated with breast cancer risk.

Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk.

It was reported that the functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase gene was associated with breast cancer risk; however, the published studies have inconsistent conclusions. To elucidate the effect of hOGG1 Ser326Cys on the susceptibility to breast cancer, all available studies were collected in this meta-analysis. We extracted the data from 10 case-control studies that were published in the PubMed database from 2003 to 2008 using the search phrases "human 8-oxoguanine DNA glycosylase, hOGG1, OGG1, OGG, polymorphism, genetic variation, and breast cancer." This meta-analysis included 4,963 breast cancer cases and 4,776 control subjects. The results showed that individuals who carrying the hOGG1 326Cys allele in the additive model did not have significantly increased risk of breast cancer compared with those carrying the 326Ser allele (P = 0.47, OR = 1.02; 95% CI = 0.96-1.09); similarly, no significant association between the hOGG1 326Cys allele and breast cancer risk was found either in the recessive genetic model (P = 0.34, OR = 1.06; 95% CI = 0.94-1.18) for Cys/Cys versus Ser/Cys + Ser/Ser, or dominant genetic model (P = 0.78, OR = 1.01; 95% CI = 0.93-1.11) for Cys/Cys + Ser/Cys versus Ser/Ser. In the stratified analysis, the meta-analysis showed the association between hOGG1 326Cys allele in the additive model and breast cancer was significant in European subjects (P = 0.04, OR = 0.71; 95% CI = 0.51-0.98), and dominant genetic model (P = 0.004, OR = 0.44; 95% CI = 0.25-0.77). However, the association was not significant between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (Asians and Americans). The meta-analysis suggested that the hOGG1 326Cys allele plays a significant protective effect to breast cancer in European women.

Melanoma commonly clusters in families, and the recent identification of numerous genotypes predicting higher risks of melanoma has led to the widespread perception that this cancer is predominantly a genetic disease. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of familial factors to melanoma, estimated by the population attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and family history of the disease; we identified 22 such studies using citation databases, followed by manual review of retrieved references. We calculated summary RRs using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. Overall, family history was associated with a significant 2-fold increased risk of melanoma (odds ratio, 2.06; 95% confidence interval, 1.72-2.45); however, there was significant heterogeneity (P = 0.01). The pooled estimate for population-based studies (n = 11) was 2.03 (1.70-2.43), and 2.51 (1.55-4.07) for clinic/hospital-based studies (n = 11), both with significant heterogeneity (P = 0.049 and P = 0.013, respectively). Two studies used record linkage to verify family history in relatives; the pooled risk estimate from these two studies was 2.52 (2.11-3.00) with no evidence of heterogeneity (P = 0.258). Estimates of PAF associated with a positive family history ranged from 0.007 for Northern Europe to 0.064 for Australia (0.040 for all regions combined). Our findings suggest that only a small percentage of melanoma cases (always <7%) are attributable to familial risk; the majority of melanomas are presumably attributable to other factors.

The functional Ser326Cys polymorphism in the human 8-oxogunaine DNA glycosylase (hOGG1) gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case-control studies, including 6,804 breast cancer cases and 6,725 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, no significant associations between the hOGG1 Ser326Cys polymorphism and breast cancer risk were found for Cys/Cys versus Ser/Ser (OR = 1.07, 95% CI: 0.94-1.20), Ser/Cys versus Ser/Ser (OR = 0.99, 95% CI: 0.91-1.07), Cys/Cys + Ser/Cys versus Ser/Ser (OR = 1.00, 95% CI = 0.93-1.08), and Cys/Cys versus Ser/Cys + Ser/Ser (OR = 1.07, 95% CI: 0.97-1.18). In the stratified analysis by ethnicity, source of controls, and menopausal status, significant associations were still not observed in all genetic models. Taken together, the results suggest that the hOGG1 Ser326Cys polymorphism is not associated with breast cancer risk.

Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of exogenous and endogenous substrates. The metabolism of polycyclic aromatic hydrocarbons and other procarcinogens through CYP1B1 may well lead to their activation. Apart from the extensively studied Val432Leu polymorphism, three single nucleotide polymorphisms in CYP1B1 have been studied concerning their potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and Asn453Ser. This meta-analysis aims to examine whether the three aforementioned polymorphisms are associated with breast cancer risk. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were 0.933 (0.808-1.078) for heterozygous and 0.819 (0.610-1.100) for homozygous Gly subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896-1.097) for heterozygous and 0.935 (0.729-1.198) for homozygous Ser subjects. With respect to Asn453Ser, the pooled ORs were 0.961 (0.906-1.019) for heterozygous and 0.984 (0.846-1.144) for homozygous Ser subjects. In conclusion, this meta-analysis suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not associated with breast cancer risk. Studies on Chinese populations are needed, to elucidate race-specific effects on East Asian populations, if any.

Published data on the association between cytochrome P-450 1A2 (CYP1A2)-164 A/C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between CYP1A2-164 A/C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC versus AA, CC versus AA), dominant model (CC + AC versus AA), and recessive model (CC versus AA + AC), respectively. A total of 9 studies including 7,580 cases and 10,020 controls were involved in this meta-analysis. Overall, no significantly elevated breast cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (AC versus AA: OR = 1.02, 95% CI = 0.92-1.13; CC versus AA: OR = 1.17, 95% CI = 0.83-1.64; dominant model: OR = 1.07, 95% CI = 0.93-1.23; and recessive model: OR = 1.13, 95% CI = 0.82-1.55). In the subgroup analysis by ethnicity or source of controls, there was still no significant association detected in all genetic models. In conclusion, upto date, there is still not enough evidence to indicate the association of CYP1A2-164 A/C polymorphism and breast cancer development.