Hereditary hemochromatosis (HH) is an autosomal recessive disorder mainly associated with homozygosity for the C282Y and H63D mutations in the hemochromatosis (HFE) gene. The reports about the C282Y and H63D mutations and hepatocellular carninoma (HCC) were controversial. To clarify the relationship between C282Y and H63D mutations and HCC, a meta-analysis including nine studies (1102 HCC cases and 3766 controls, mainly came from European populations) was performed.

The common functional CYP2E1 Rsa I/Pst I polymorphism may influence the risk of esophageal cancer. However, the published results are conflicting. We therefore conducted a meta-analysis comprised of 11 published case-control studies with 1,088 cases and 2,238 controls. Odds ratios (ORs) with 95% confidence interval (CIs) were used to assess the strength of the association. Overall, the pooled ORs were 0.53 (95% CI = 0.31-0.89, P (heterogeneity) < 0.001) and 0.57 (95% CI = 0.34-0.96, P (heterogeneity) < 0.001), for the heterogeneity c1/c2 and c2 allele carriers (c1/c2 + c2/c2) compared with the homozygous c1/c2, respectively. In subgroup analysis by race, the same significant risks were found among Asians (for c2 vs. c1: OR = 0.64, 95% CI = 0.43-0.95, P (heterogeneity) < 0.001; for c1/c2 vs. c1/c1: OR = 0.48, 95% CI = 0.28-0.82, P (heterogeneity) < 0.001; for c1/c2 + c2/c2 vs. c1/c1: OR = 0.51, 95% CI = 0.30-0.86, P (heterogeneity) < 0.001). In conclusion, our meta-analysis demonstrates that CYP2E1 Rsa I/Pst I c2 allele may be a decreased risk factor for developing esophageal cancer among Asians populations.

To examine the association between CYP1A1 polymorphisms (MspI and Ile/Val) and esophageal cancer (EC) by systematically reviewing the risk of the original studies.

We identified a set of genes with an unexpected bimodal distribution among breast cancer patients in multiple studies. The property of bimodality seems to be common, as these genes were found on multiple microarray platforms and in studies with different end-points and patient cohorts. Bimodal genes tend to cluster into small groups of four to six genes with synchronised expression within the group (but not between the groups), which makes them good candidates for robust conditional descriptors. The groups tend to form concise network modules underlying their function in cancerogenesis of breast neoplasms.

We performed a meta-analysis to assess whether MC1R variants increase the risk of melanoma in CDKN2A mutation carriers of melanoma-prone families.

To derive a more precise estimation of the relationship between the slow or rapid acetylation resulting from N-acetyltransferase 2 (NAT2) polymorphisms and breast cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of association. The pooled ORs were performed for slow versus rapid acetylation genotypes. A total of 26 studies including 9,215 cases and 10,443 controls were included in the meta-analysis. Overall, no significantly elevated breast cancer risk was associated with NAT2 slow genotypes when all studies were pooled into the meta-analysis (OR = 1.026, 95% CI = 0.968-1.087). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR = 1.001, 95% CI = 0.938-1.068) or Asians (OR = 1.155, 95% CI = 0.886-1.506). When stratified by study design, statistically significantly elevated risk associated with NAT2 slow genotypes was only found among hospital-based studies (OR = 1.178, 95% CI = 1.037-1.339). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found in either premenopausal (OR = 1.053, 95% CI = 0.886-1.252) or postmenopausal women (OR = 0.965, 95% CI = 0.844-1.104). When stratified by cumulative smoking exposure, in the subgroup of smokers with high pack-years, NAT2 slow genotypes were significantly associated with increased breast cancer risk (OR = 1.400, 95% CI = 1.099-1.784). In conclusion, this meta-analysis suggested that there is overall lack of association between NAT2 genotypes and breast cancer risk, however, NAT2 polymorphisms when combining with heavy smoking history may contribute to breast cancer susceptibility.

It was expected that with the advent of genomics, oncology may defeat the deadliest forms of cancer including malignant melanoma, but the past years have indicated that this is not the case. Despite the stunning success of genomics in defining markers or gene signatures for breast cancer prognosis and predicting therapies, there is virtually no progression in malignant melanoma. This is happening when experimental oncology or metastasis research is using several rodent and human melanoma models, when our knowledge on the metastatic cascade is actually derived from these models. Our critical analysis of these studies revealed several factors which might be responsible for this failure. First, it is evident, that these studies must be based on rigorous sample collection and basic pathological considerations, where divergent histological types of melanoma cannot be analysed universally. Secondly, without following basic consideration of metastasis biology, the majority of these studies were rarely based on primary tumors but frequently on various types of regional metastases. Third, successful expression profiling studies on other tumors such as breast cancer, provided evidences that the homogeneity of the patient cohort at least by clinicopathological stage is a critical element when defining prognostic signatures. Four studies attempted to define the prognostic signature of skin melanoma but only one based the study on the primary tumor resulting in heterogenous signatures with a minimal overlap (MCM3 and NFKBIZ). Four study attempted to define the invasiveness-signature in the primary tumor based on thickness or growth pattern discrimination identifying a 9-gene overlap which proved to be different from the prognostic signatures. On the other hand, seven studies analyzed various types of metastatic tissues (rarely visceral-, mostly cutaneous or lymphatic metastases) to define the metastasis-signatures, again with minimal overlap (AQP3, LGALS7 and SFN). Using seven GEO-based melanoma datasets we have performed a meta-analysis of the metastasis-gene signatures using normalization protocols. This analysis identified a 350-gene signature, the core of which was a 17-gene signature characterizing locoregional metastases where the individual components occurred in 3 studies: several members of this signature were extensively studied before in context of melanoma metastasis including WNT5A, EGFR, BCL2A1 and OPN. These data suggest that only efficient inter-disciplinary collaboration throughout genomic analysis of human skin melanoma could lead to major advances in defining relevant gene-sets appropriate for clinical prognostication or revealing basic molecular pathways of melanoma progression.

Several potentially functional polymorphisms of CASP8 encoding an apoptotic enzyme, caspase 8, have been implicated in cancer risk, but individually published studies showed inconclusive results. We performed a meta-analysis of 23 publications with a total of 55 174 cancer cases and 59 336 controls from 55 individual studies. We summarized the data on the associations between three studied CASP8 polymorphisms (G>C D302H, -652 6N del and Ex14-271A>T) and cancer risk and performed subgroup analysis by ethnicity, cancer type, study design and etiology. We found that D302H CC and CG variant genotypes were associated with significantly reduced overall risk of cancers using conservative random genetic models [homozygote comparison: odds ratios (OR) = 0.79; 95% confidence interval (CI): 0.69-0.92; dominant comparison: OR = 0.93, 95% CI: 0.89-0.98; recessive comparison: OR = 0.81, 95% CI: 0.71-0.93). In further stratified analyses, the reduced cancer risk remained for subgroups of Caucasians, breast or estrogen-related cancers, and hospital- or population-based studies, except for an elevated risk for brain tumors. Similarly, the -652 6N del polymorphism was also associated with significantly reduced overall risk of cancers (homozygote comparison: OR = 0.84, 95% CI: 0.75-0.94; dominant comparison: OR = 0.88, 95% CI: 0.81-0.96; recessive comparison: OR = 0.90, 95% CI: 0.82-0.99) and all subgroups analyzed. However, the Ex14-271A>T polymorphism did not appear to have an effect on cancer risk. These results suggest that CASP8 D302H and -652 6N del polymorphisms are potential biomarkers for cancer risk.

Breast cancer is the most prevalent cancer worldwide. Many published articles have evaluated the association between the transforming growth factor beta 1 (TGFB1) T29C polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 12 studies including 10,417 breast cancer cases and 11,455 controls were identified. Overall, no significant associations between the TGFB1 T29C polymorphism and breast cancer risk were found for CC versus TT (OR = 1.00, 95% CI = 0.92-1.09), TC versus TT (OR = 0.98, 95% CI = 0.93-1.05), CC/TC versus TT (OR = 0.99, 95% CI = 0.93-1.05), and CC versus TC/TT (OR = 1.00, 95% CI = 0.93-1.08). In the subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in all genetic models. In conclusion, the present meta-analysis suggests that the TGFB1 T29C polymorphism is not a low-penetrant risk factor for developing breast cancer.

There are increasing evidences that HSD17B1 plays a significant role in the development of breast cancer. However, published data on the association between HSD17B1 Ser312Gly polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of this relationship, a meta-analysis including 9 studies with 31,053 subjects was performed in this study. Crude ORs with 95% CIs were used to assess the strength of association between HSD17B1 Ser312Gly polymorphism and breast cancer risk. The pooled ORs were performed for codominant model (Gly/Gly versus Ser/Ser, Gly/Ser versus Ser/Ser), dominant model (Gly/Gly + Gly/Ser versus Ser/Ser), and recessive model (Gly/Gly versus Gly/Ser + Ser/Ser), respectively. Overall, no significant associations were detected between HSD17B1 Ser312Gly polymorphism and breast cancer susceptibility. However, in the stratified analysis by ethnicity, significant associations were observed in Caucasians for Gly/Gly versus Ser/Ser (OR = 0.91; 95% CI 0.83-1.00), Gly/Ser versus Ser/Ser (OR = 0.92; 95% CI 0.85-0.99), and Gly/Gly + Gly/Ser versus Ser/Ser (OR = 0.92; 95% CI 0.86-0.98). In conclusion, this study suggests that HSD17B1 312Gly allele may be a protective factor for breast cancer development in Caucasians. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

NBS1 gene plays an important role in DNA repair. Many epidemiological studies have investigated the association between NBS1 8360G > C polymorphism and breast cancer, however, the results are still controversial. Therefore, we performed a meta-analysis of 10 case-control studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The results showed NBS1 8360G > C polymorphism contributed to breast risk in overall populations (for CC vs. GG: OR = 0.75, 95% CI = 0.74-0.98, P = 0.13 for heterogeneity; for the recessive model CC vs. GG/CG: OR = 0.88, 95% CI = 0.77-1.00, P = 0.44 for heterogeneity). In subgroup analysis by ethnicity, no significant association was found in all genetic models. In summary, our meta-analysis strongly suggests the NBS1 8360G > C polymorphism is associated with breast cancer.

Published data on the association between MnSOD Val16Ala 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 the MnSOD Val16Ala polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Val/Ala vs. Val/Val, Ala/Ala vs. Val/Val), dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val), respectively. A total of 32 studies including 26,022 cases and 32,426 controls were involved in this meta-analysis. Overall, no significant associations were found between MnSOD Val16Ala polymorphism and breast cancer risk when all studies pooled into the meta-analysis (Val/Ala vs. Val/Val: OR = 1.022, 95% CI = 0.981-1.064; Ala/Ala vs. Val/Val: OR = 1.006, 95% CI = 0.934-1.083; dominant model: OR = 1.013, 95% CI = 0.962-1.066; and recessive model: OR = 0.985, 95% CI = 0.931-1.042). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MnSOD Val16Ala polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Published data on the association between TGFB1 L10P polymorphism and breast cancer risk are inconclusive. In order 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 30 studies including 20,401 cases and 27,416 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TGFB1 10P allele when all studies were pooled into the meta-analysis (LP vs. LL: OR = 1.046, 95% CI = 1.003-1.090; dominant model: OR = 1.052, 95% CI = 1.012-1.095). In the subgroup analysis by ethnicity, statistically significantly elevated risk was found in Caucasians (dominant model: OR = 1.045, 95% CI = 1.001-1.091). When stratified by study design, statistically significantly elevated risk was found based on population-based studies (dominant model: OR = 1.076, 95% CI = 1.019-1.136). In conclusion, this meta-analysis suggests that the TGFB1 10P allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Published data on the association between MTHFR C677T 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 the MTHFR C677T polymorphism and breast cancer risk. The pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A total of 37 studies including 15,260 cases and 20,411 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TT variant genotype in homozygote comparison and dominant genetic model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11, 95% CI = 1.01-1.23; dominant model: OR = 1.04, 95% CI = 1.00-1.09). In the subgroup analysis by ethnicity, significantly increased risks were found for TT allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04-1.35; recessive model: OR = 1.15, 95% CI = 1.03-1.29). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TT vs. CC: OR = 1.18, 95% CI = 1.02-1.38; recessive model: OR = 1.17, 95% CI = 1.05-1.29). In the subgroup analysis by menopausal status, statistically significantly increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI = 1.02-1.23; dominant model: OR = 1.11, 95% CI = 1.01-1.22). In conclusion, this meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for developing breast cancer.

To summarize existing evidence about whether the presence of mutant or upregulated p53 is a prognostic factor for patients presenting with squamous cell carcinoma arising from the larynx, oropharynx, hypopharynx, or oral cavity.

Published data on the association between BRCA2 N372H 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 22 studies including 22,515 cases and 22,388 controls were involved in this meta-analysis. Overall, no significant associations were found between BRCA2 N372H polymorphism and breast cancer risk when all studies pooled into the meta-analysis (NH versus NN: OR = 1.01, 95% CI = 0.97-1.05; HH versus NN: OR = 1.05, 95% CI = 0.97-1.13; dominant model: OR = 1.01, 95% CI = 0.98-1.05; and recessive model: OR = 1.05, 95% CI = 0.98-1.13). In the subgroup analysis by ethnicity, still no significant associations were found for Caucasians, Asians, or Africans. When stratified by study design, statistically significantly elevated risk was found for 372H allele based on population-based studies (HH versus NN: OR = 1.11, 95% CI = 1.01-1.21; dominant model: OR = 1.05, 95% CI = 1.00-1.10; recessive model: OR = 1.09, 95% CI = 1.00-1.18). In conclusion, this meta-analysis suggests that the BRCA2 372H allele may be a low-penetrant risk factor for developing breast cancer. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been widely reported, but results were inconsistent and underpowered. To clarify the effects of MTHFR polymorphisms on the risk of breast cancer, an updated meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of breast cancer was conducted. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to January 2010. Finally, a total of 41 studies with 16,480 cases and 22,388 controls were included, all for C677T polymorphism and 20 with 12,170 cases and 15,865 controls for A1298C polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model, and recessive genetic model, respectively. Subgroup analyses were also performed by ethnicity and menopausal status. With respect to C677T polymorphism, significantly elevated breast cancer risk was found in overall analysis (T vs. C: OR = 1.041, 95% CI = 1.009-1.073; TT vs. CC: OR = 1.132, 95% CI = 1.019-1.259; TT vs. CC + CT: OR = 1.119, 95% CI = 1.014-1.236); in the subgroup analysis by ethnicity, significantly increased risk was found in East Asian population (T vs. C: OR = 1.121, 95% CI = 1.016-1.237; TT vs. CC: OR = 1.331, 95% CI = 1.073-1.650; TT vs. CC + CT: OR = 1.265, 95% CI = 1.058-1.513) but not in Caucasian population; in the subgroup analysis by menopausal status, no statistically significant association was found. With respect to A1298C polymorphism, no significant association with breast cancer risk was demonstrated in overall, ethnicity- and menopausal status-based population. It can be concluded that potentially functional MTHFR C677T polymorphism may play a low penetrance role in the development of breast cancer.

Prostate stem cell antigen (PSCA), a member of the LY-6/Thy-1 family of glycosylphosphatidylinositol-anchored cell surface proteins, is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type. Therefore, this study was to investigate whether these 2 SNPs were associated with the risk of gastric cancer in Chinese population. We genotyped rs2976392 and rs2294008 in PSCA in a case-control study including 1,053 incident gastric cancer patients and 1,100 cancer-free controls in a high-risk Chinese population. We found that variant genotypes of rs2976392 (GA/AA) were associated with a significantly 37% increased risk of gastric cancer (adjusted OR =1.37, 95% CI = 1.15-1.62), compared with variant homozygote GG, and the associations were all consistently significant in both intestinal and diffuse subtypes, and among different subgroups stratified by age, sex, drinking or smoking status. Interestingly, a significant multiplicative interaction between rs2976392 (GA/AA) and alcohol drinking was detected on the development of intestinal-type gastric cancer (p = 0.009). However, rs2294008 variant genotypes (CT/TT) were associated with a nonsignificant increased risk of gastric cancer (adjusted OR = 1.14, 95% CI = 0.96-1.36). A small meta-analysis including 5 case-control studies showed undoubtedly associations between PSCA rs2294008 and rs2976392 and gastric cancer risk (OR = 1.83, 95% CI: 1.29-2.60 and OR = 1.84, 95% CI: 1.33-2.56, respectively). These findings provide further evidence supporting that the genetic variants of PSCA gene may contribute to the gastric carcinogenesis.

The Catechol-O-methyltransferase (COMT) plays an important role in the development of breast cancer. Many previous epidemiologic studies explored the association of COMT Val158Met polymorphism with breast cancer susceptibility. However, the results were inconsistent. We therefore performed a meta-analysis of 26 published studies including 16,693 breast cancer patients and 18,261 healthy controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association of the COMT Val158Met polymorphism with breast cancer risk. No significant association was found in all genetic models in overall, Asian, European populations. After the studies whose genotype frequencies in the controls did not fulfill Hardy-Weinberg equilibrium were excluded, we found a borderline significant decreased breast cancer risk among Europeans (for the recessive model LL versus HH/HL: OR = 0.90, 95% CI = 0.90-1.00, P (heterogeneity) = 0.33). There was no between-study heterogeneity. In conclusion, COMT Val158Met polymorphism may be a low-penetrant risk factor for breast cancer development in European population.

Several common single-nucleotide polymorphisms (SNPs) within the XRCC2 gene have been identified as potential breast cancer susceptibility loci and a coding SNP in exon 3 (Arg188His, rs3218536) has been extensively studied, though the results were inconclusive. We, in this study, performed a more convincing and precise estimation of the relationship between Arg188His and breast cancer by meta-analyzing the currently available evidence from literature. A total of 16 studies involving 18,341 cases and 19,028 controls (37,369 subjects) were identified for meta-analysis. 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. When all the studies were pooled into meta-analysis, there was no evidence of a significant association between Arg188His and breast cancer risk in any genetic models. Notably, Arg188His tended to be related to breast cancer in a fixed-effects, dominant model (OR = 0.922, 95% CI: 0.870-0.978, P = 0.007); however, since there was a between-study heterogeneity (P (h) = 0.014), we assessed the association using a random-effects model instead and no significance was observed (OR = 0.932, 95% CI: 0.852-1.020, P = 0.128). Subgroup analysis by ethnicity did not change the results. In summary, the present meta-analysis suggests that the XRCC2 Arg188His is not directly associated with breast cancer risk. However, considering that susceptibility is likely to be the result of a complex interplay between genetic variation and environmental factors, we cannot rule out the possibility of interactions between Arg188His and other variants. Further investigation on the influence of this SNP in modifying the relationship between environment exposures and breast cancer risk is still needed.