Hsa-mir-499 rs3746444 polymorphism and cancer risk: a meta-analysis

MicroRNAs(miRNAs) are gene regulators involved in numerous diseases including cancer,heart disease,neurological disorders,vascular abnormalities and autoimmune conditions.Although hsa-mir-499 rs3746444 polymorphism was shown to contribute to the susceptibility of multiple genes to cancer,the data have yielded conflicting results.Therefore,this meta-analysis was performed to provide a comprehensive assessment of potential association between hsa-mir-499 rs3746444 polymorphism and cancer risk.In this meta-analysis,a total of 9 articles regarding 10 eligible case-control studies in English(including 6134 cases and 7141 controls) were analyzed.No significant association between hsa-mir-499 rs3746444 polymorphism and overall cancer risk was demonstrated.However,an increased risk was observed in the subgroup of breast cancer patients(G allele vs A allele:OR = 1.10,95% CI = 1.00-1.20;P heterogeneity = 0.114;I 2 = 53.9%) and population-based studies(G allele vs A allele:OR = 1.12,95% CI = 1.00-1.25;P heterogeneity = 0.062;I 2 = 64.0%).The findings suggested an association between hsa-mir-499 rs3746444 polymorphism and increased risk to breast cancer.     

Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry

The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5; P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P=0.5). These findings suggest that although the more common c.1066-6T>G variant is not associated with breast cancer, the rare ATM c.7271T>G variant is associated with a substantially elevated risk. Since c.7271T>G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population.     

细胞毒T淋巴细胞相关抗原4基因多态性与乳腺癌易感性的关联研究

目的: 探讨CTLA-4基因多态性位点-1722T/C和CT60G/A与中国北方汉族妇女乳腺癌易感性的关系.方法: 采用聚合酶链反应(PCR)和限制性片段长度多态性方法, 对328例中国北方汉族乳腺癌患者和327例正常对照者进行CTLA-4基因-1722位点和CT60位点多态性检测. 结果: 乳腺癌患者CTLA-4基因CT60位点G等位基因频率在乳腺癌患者组中明显高于正常对照组(28.7% 比23.5%; P=0.0352, OR=1.30, 95% CI=1.02～1.67); -1722C-CT60A单体型在对照组中的频率大于病例组中的频率, 有明显差异(P=0.0283, OR=0.77, 95% CI=0.97～0.61), 而在-1722位点基因型频率、等位基因频率与对照组比较差异无统计学意义(P＞0.05).结论: CTLA-4基因多态性-1722和CT60两个位点与我国北方汉族妇女乳腺癌发病存在一定的相关性.     

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.     

The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis

Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic properties and play an important role in the pathogenesis of cancer. IL-10-1082A>G polymorphism is the most extensively studied polymorphism in the IL-10 gene in cancer susceptibility. To date, a number of case-control studies were conducted to investigate the association between IL-10-1082A>G polymorphism and cancer risk in humans. However, the association between the IL-10-1082A>G polymorphism and cancer risk is still ambiguous. In an effort to solve this controversy, we performed a meta-analysis based on 61 case-control studies, including 14,499 cancer cases and 16,967 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. In the stratified analyses by specific cancer type, increased risk was found in lung cancer (OR = 3.16, 95% CI = 1.16-8.63 for GA versus AA; OR = 2.07, 95% CI = 1.16-3.70 for GG versus AA; OR = 3.17, 95% CI = 1.31-7.68 for GA/GG versus AA) and non-Hodgkin's lymphoma (OR = 1.18, 95% CI = 1.02-1.36 for GA versus AA; OR = 1.17, 95% CI = 1.02-1.35 for GA/GG versus AA). The meta-analysis also indicated that the variant genotypes were associated with a moderately increased risk in Asians in all genetic models (OR = 1.80, 95% CI = 1.17-2.76 for GA versus AA; OR = 3.32, 95% CI = 1.62-6.82 for GG versus AA; OR = 1.67, 95% CI = 1.07-2.60 for GA/GG versus AA; OR= 2.93, 95% CI = 1.43-6.03 for GG versus AA/GA). The meta-analysis suggested that the IL-10-1082A>G polymorphism was associated with increased risk of cancer in Asians and lung cancer and non-Hodgkin's lymphoma. To draw comprehensive and true conclusions, more researches with larger numbers of worldwide participants are needed to examine associations between IL-10-1082A>G polymorphism and cancer risk.     

The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis

Inter-individual differences in susceptibility to breast cancer are partially mediated through the levels of endogenous and exogenous steroid hormones. The CYP17 gene encodes P450c17alpha, an enzyme that is involved in the metabolism of steroid hormones. Increased endogenous steroid hormone levels have been associated with a MspA1 polymorphism in the 5'-promoter region of the CYP17 gene. The CYP17 MspA1 polymorphism has been postulated as being associated with the risk of developing breast cancer. However, the association between the CYP17 MspA1 polymorphism and breast cancer risk has been controversial in the literature. To re-examine this controversy, we have undertaken a meta-analysis of 15 case-control studies, which included a total of 4227 breast cancer cases and 4730 individual controls. The odds ratio (OR) was used to evaluate the risk of breast cancer for each study, using homozygosity of the wild-type allele as the control group. Statistical analysis showed no evidence of heterogeneity within the studies. The pooled ORs of breast cancer associated with the combined variant (A1/A2 + A2/A2) and the homozygous genotype (A2/A2) were 0.98 (95% CI 0.89-1.07) and 1.05 (95% CI 0.87-1.21), respectively. Similarly, the pooled ORs of advanced breast cancer associated with the combined variant and the homozygous genotype were 0.96 (95% CI 0.77-1.20) and 0.88 (95% CI 0.55-1.41), respectively. A pooling of the studies was also conducted for the various ethnic groups, but failed to show an association of CYP17 MspA1 polymorphism with breast cancer risk in the different ethnic groups. In addition, our results show that a possible protective effect for breast cancer risk of a later age at menarche was mainly limited to women with the A1 homozygous genotype. The OR for age at menarche (> or = 13) was 0.87 (95% CI 0.62-1.17). Our results suggest that CYP17 MspA1 polymorphism may be at best a weak modifier of breast cancer risk but is not a significant independent risk factor.     

Cytochrome P450 1A1 (<Emphasis Type="Italic">CYP1A1</Emphasis>) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis

The cytochrome P450 1A1 gene (CYP1A1), encoding Phase I metabolic enzymes, appeared to be a candidate gene for breast cancer risk. However, studies on the association between polymorphisms in this gene and breast cancer have yielded conflicting results. We performed a meta-analysis to investigate the association with breast cancer of the CYP1A1 polymorphisms T3801C (9,316 cases and 12,714 controls) and A2455G (9,552 cases and 9,320 controls). In the genotype contrast of A2455G, both additive [GG vs AA, P = 0.04, fixed-effects OR 0.72; 95% CI (0.53–0.99), P = 0.95 for heterogeneity] and recessive [GG vs (GA + AA), P = 0.04, fixed-effects OR 0.73; 95% CI (0.53–0.99), P = 0.97 for heterogeneity] models produced significant results in east-Asians. In pre-menopausal women in a worldwide population, significant association between A2455G and breast cancer was also found using both models [additive model: P = 0.02, fixed-effects OR 0.52; 95% CI (0.29–0.92), P = 0.39 for heterogeneity; recessive model: P = 0.02, fixed-effects OR 0.51; 95% CI (0.29–0.90), P = 0.38 for heterogeneity]. Our meta-analysis suggests that an A2455G G/G genotype is associated with a trend of reduced breast cancer risk, both in east-Asian women and in pre-menopausal women worldwide, while the T3801C C allele might not be a risk factor for breast cancer. Larger scale primary studies are required to further evaluate the interaction of CYP1A1 polymorphisms and breast cancer risk in specific populations.     

Tumor necrosis factor-α gene 308G/A polymorphism is not associated with esophageal squamous cell carcinoma risk in Kazakh patients

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with a strong tendency toward familial aggregation and a higher incidence as well as mortality in Kazakh population. Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that plays a role in controlling the progression of lung cancer, hepatocellular cancer, breast cancer and gastric cancer. But the association between TNF-α-308G/A and ESCC still remains unclarified. Materials and Methods: Here, we investigated the potential associations between the TNF-α-308G/A and susceptibility to ESCC in 212 cases and 200 controls from a pure ethnic population of Kazakh. DNA extraction and Real-time PCR were performed to detect the TNF-α-308G/A expression levels and odd ratios (ORs) with the corresponding 95% confidence interval (CI) were to evaluate their association with TNF-α-308G/A polymorphism. Results: We found that the frequencies of TNF-α-308G/A in the cases were similar to that of the controls with no differences being statistically significant (χ²=1.23, P>0.05). Using the G allele as the reference genotype, individuals who carried A allele had a significantly increased risk of developing ESCC (OR=2.64, 95% CI=1.31~5.35). Especially, the G/A+A/A genotype are associated with increased risk of metastatic as compared with GG genotype individuals (OR=2.08, 95% CI=1.14-3.80, P=0.02). Conclusions: Our findings suggest that though the TNF-α-308G/A polymorphism may not be correlated with the susceptibility to Kazakh’s ESCC in Xinjiang, patients who carry A allele tend to poorly differentiated and lymph node metastasis.     

Association of CAV1 polymorphisms with the risks of breast cancer: A systematic review and meta-analysis

BackgroundCaveolin-1 (CAV1) polymorphisms have been shown to correlated with breast cancer risk in previous studies. However, the role of CAV1 polymorphisms still remained indecisive, and dual functions of CAV1 was demonstrated in breast cancer development. Consequently, a meta-analysis to evaluate and summarize the association of the CAV1 polymorphisms with breast cancer susceptibility.Material and methodsExtensive search was performed in PubMed, Web of Science, Google scholar, EMBASE.com, CNKI and Wanfang searching platform up to March 2019. The Newcastle–Ottawa Scale (NOS) were used to evaluate the quality of each study. The Odds ratios (ORs) and the 95% confidence intervals (CIs) were analyzed to evaluate the strength of the associations in five genetic models. Inter-study heterogeneity was quantified using the I-squared (I²) test. In addition, the Egger’s test and Begg’s test were applied to evaluate the publication bias.Results4 case-control studies with 2115 cases and 2138 controls were enrolled into this analysis. There was a significant association between rs3807987 polymorphism of CAV1 and breast cancer in allele comparison (A vs. G: OR = 1.288, 95％CI = 1.162–1.428, P < 0.001), heterozygote comparison (AG vs. GG: OR= 1.422, 95％CI=1.233–1.639, P < 0.001), and dominant comparison (AA+AG vs. GG: OR=1.395, 95％CI=1.228-1.586, P < 0.001). A significant association of rs3807987 polymorphism in allele comparison (A vs. G: OR=1.238, 95％CI=1.109–1.383, P < 0.001), heterozygote comparison (AG VS. GG: OR=1.466, 95％CI=1.267–1.697, P < 0.05), and dominant comparison (AA+AG vs. GG: OR=1.384, 95％CI=1.209–1.585, P < 0.001) was also founded amongst Chinese population. A significant association between rs7804372 polymorphism and breast cancer amongst Chinese population in recessive comparison (AA vs. AT + TT: OR = 0.730, 95％CI = 0.567–0.940, P = 0.015) was identified. No significant association between breast cancer risk and rs1997623 was found.ConclusionCAV1 rs3807987 and rs7804372 polymorphisms are associated with the change of breast cancer risk. More well-designed and large studies in various populations are needed to further elaborate these associations.     

The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis

DNA mismatch repair, known as a fundamentally biological pathway, plays key roles in maintaining genomic stability, eliminating mismatch bases and preventing both mutagenesis in the short term and cancerogenesis in the long term. Polymorphisms of MLH1 in individuals may have an effect on the DNA repair capacity and therefore on cancer risk. Recently, emerging studies have been done to evaluate the association between MLH1 -93 G/A polymorphism and cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. In this meta-analysis, we assessed reported studies of association between the MLH1 -93 G/A polymorphism and cancer risk including 13?691 cancer cases and 14?068 controls from 17 published studies. A borderline significant association between the MLH1 -93 G/A polymorphism and cancer risk was observed in overall analysis [heterozygote: odds ratio (OR) = 1.15; 95% confidence interval (CI) 1.05-1.26; homozygote: OR = 1.21; 95% CI, 1.04-1.40; dominant model: OR = 1.13; 95% CI 1.01-1.26; recessive model: OR = 1.21; 95% CI 1.07-1.35, respectively]. In subgroup analysis by ethnicity, significantly increased risks were found in Asian population and mixed population but not in Caucasian population. After stratified analysis according to the quality of literature, increased cancer risks were observed in the studies of lower quality but not in the studies of higher quality. Similarly, elevated cancer risks were observed in hospital-based studies but not in population-based studies. These findings showed no persuasive evidence that MLH1 -93 G/A polymorphism was associated with an increased risk of cancer. On the conservative standpoint, well-designed population-based studies with larger sample size in different ethnic groups should be performed to further confirm these results.     

Meta-Analysis of Adiponectin Polymorphisms and Colorectal Cancer Risk

Objective The adiponectin gene (ADIPOQ) has been suggested to be associated with the pathogenesis of colorectal cancer (CRC). However, the results have been inconsistent. In this study, we performed a meta-analysis to investigate the association between adiponectin polymorphisms and CRC risk.Methods All eligible case-control studies published up to March 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model.Results A total of 9 case-control studies were included, Of those studies, there were eight studies (2024 cases and 2777 controls) for rs1501299G/T polymorphism, five studies (1401 cases and 1691 controls) for rs2241766T/G polymorphism, five studies (2945 cases and 3361 controls) for rs266729C/G polymorphism, three studies (1221 cases and 1579 controls) for rs822395A/C polymorphism and three studies (1222 cases and 1575 controls) for rs822396A/G polymorphism. Overall, a significant association was observed for rs2241766T/G polymorphism under heterozygote comparison (TG vs. TT: OR=1.22, 95%CI: 1.05-1.43); while there was no significant association for rs2241766 polymorphism under other genetic models, and for other four polymorphisms under all genetic models. Besides, when stratified analyses by ethnicity, no significant association between five polymorphisms and CRC risk were observed under all genetic models among Asian, Caucasian and African-American.Conclusions This meta-analysis indicated that adiponectin rs2241766T/G rather than rs1501299G/T, rs266729C/G, rs822395A/C and rs822396A/G polymorphism was associated with the risk of colorectal cancer.     

Tumour necrosis factor alpha -308G/A polymorphism and risk of the four most frequent cancers: a meta-analysis

The latest data show that breast, prostate, lung and colorectal cancer are the four most frequent cancers in both sexes worldwide. A number of molecular epidemiological studies have been conducted to examine the association between TNF alpha -308G/A and the risk of those cancers. However the results have been inconclusive or inconsistent. We then performed a meta-analysis to derive a precise estimation of this association. We carried out a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database for studies using related keywords. The inclusion criteria were (i) in English or Chinese; (ii) case-control study on this association; (iii) provide usable genotype frequencies; and (iv) sufficient published data for estimating an odds ratio (OR) with 95% confidence interval (CI). ORs and 95% CIs were calculated to assess the strength of this association under homozygote comparison (AA vs GG), heterozygote comparison (GA vs GG), dominant (AA/GA vs GG) and recessive (AA vs GA/GG) genetic model comparison. Thirty case-control studies with a total number of 16,507 cases and 19,749 controls were selected for analysis. Overall, no significant association was found between this polymorphism and the risk of total four cancers (GA vs GG: OR=1.02, 95% CI=0.91-1.14, P=0.78). However, there was a significant association between this polymorphism and breast cancer risk in western populations (GA vs GG: OR=0.91, 95% CI=0.85-0.96, P=0.002). This meta-analysis also revealed that this polymorphism was not associated with susceptibility to the other three cancers.     

Genetic polymorphisms of TP53-binding protein 1 (TP53BP1) gene and association with breast cancer risk

In the present study, we evaluated the association between the TP53BP1 Glu353Asp and T-885G polymorphisms and breast cancer risk as well as with the clinicopathological characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using PCR-RFLP method in a hospital-based Malaysian population. Breast cancer risk was not observed among women who were heterozygous (OR(adj) = 0.887; 95% CI, 0.632-1.245) or homozygous (OR(adj) = 1.083; 95% CI, 0.595-1.969) for Asp allele, and those carriers of Asp allele (OR(adj) = 0.979; 95% CI, 0.771-1.243). Similarly, women who were TG heterozygotes (OR(adj) = 1.181; 95% CI, 0.842-1.658) or GG homozygotes (OR(adj) = 1.362; 95% CI, 0.746-2.486) and carriers of G allele (OR(adj) = 1.147; 95% CI, 0.903-1.458) were not associated with increased risk of breast cancer. Asp allele genotype was significantly associated with ER negativity (p = 0.0015) and poorly differentiated tumours (p = 0.008), but G allele genotype was not associated with the clinicopathological characteristics. In conclusion, Glu353Asp and T-885G polymorphic variants might not have an influence on breast cancer risk, thus might not be potential candidates for cancer susceptibility. Glu353Asp variant might be associated with tumour aggressiveness as defined by its association with ER negativity and poorly differentiated tumours.     

The association between CD209 gene polymorphisms and pulmonary tuberculosis susceptibility: a meta-analysis

Aim: Three common polymorphisms in CD209 gene (-336A/G, -871A/G and -139G/A) have been reportedly associated with pulmonary tuberculosis risk. However, the findings from different studies were inconsistent. Therefore, we conducted a comprehensive meta-analysis to determine the association between CD209 gene polymorphisms and pulmonary tuberculosis susceptibility. Methods: The PubMed, SCI and Elsevier were searched up to April 18, 2015 for studies on the association of CD209 gene polymorphisms and pulmonary tuberculosis. Pooled odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated in a fixed-effects or random-effects model. Results: Twelve case-control studies with 3114 cases and 3088 controls were included. For -871A/G mutation, significant decreased pulmonary tuberculosis risk was observed in allele model (G vs. A: P = 0.009; OR = 0.70, 95% CI = 0.54-0.92), heterozygous model (AG vs. AA: P = 0.009; OR = 0.59, 95% CI = 0.40 to 0.88) and dominant model (AG+GG vs. AA: p =0.01; OR = 0.61, 95% CI = 0.42 to 0.89). For -336A/G polymorphism, no associations were found in all genetic models. In the subgroup analysis by ethnicity, statistical association was observed for Asians in GG vs. AA (P = 0.04; OR = 2.31, 95% CI = 1.05-5.09). No significant association was identified between -139G/A variation and pulmonary tuberculosis risk. Conclusions: This meta-analysis provides evidences that CD209 gene -871A/G is associated with decreased susceptibility to pulmonary tuberculosis in overall population; -336A/G polymorphism is associated with increased susceptibility of pulmonary tuberculosis in Asians. However, the -139G/A polymorphism is not associated with susceptibility to pulmonary tuberculosis.     

Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk

Several different genetic variants at chromosome 8q24 have been related to prostate, breast and colorectal cancer risk with evidence of region-specific risk differentials for various tumor types. We investigated the association between 15 polymorphisms located in 8q24 regions associated with cancer risk in a pooled analysis of 2587 colorectal adenoma cases, 547 colorectal cancer cases and 2798 controls of European descent from four studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations. Three polymorphisms (rs10808555, rs6983267 and rs7837328) located between 128.47 and 128.54 Mb were found to be associated with colorectal tumor risk. The association was strongest for the previously reported rs6983267 variant and was similar for both adenoma (OR(per allele) = 1.16, 95% CI: 1.07-1.25, P = 0.0002) and cancer (OR (per allele) = 1.17, 95% CI: 1.01-1.35, P = 0.03). The strength of the association of the regional haplotype containing variant alleles at rs10808555, rs6983267 and rs7837328 but not rs10505476 was greater than that of any single variant of both adenoma (OR = 1.27, P = 0.0001) and cancer (OR = 1.26, P = 0.03). The risk associated with rs6983267 was stronger for multiple adenomas (OR(per allele) = 1.29, P = 5.6 x 10(-6)) than for single adenoma (OR(per allele) = 1.10, P = 0.03) with P(heterogeneity) = 0.008. This study confirms the association between colorectal neoplasia and the 8q24 polymorphisms located between 128.47 and 128.54 Mb and suggests a role for these variants in the formation of multiple adenomas.     

Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes

The cytochrome P450 family (CYPs) and the glutathione S-transferase (GSTs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. In this study we examine the role of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk in Brazilian women. The study population consisted of 102 incident breast cancer cases and 102 healthy controls. Genotyping analyses were performed by PCR-based methods. A significant finding was observed between GSTP1 Ile-Val polymorphism and breast cancer risk (OR = 1.81; CI 95% = 1.04-3.16). A significant association was observed between women with 0-2 risk genotypes and those with 4 or more risk genotypes (OR = 2.42; CI 95% = 1.13-5.18) when the potential combined effects of the risk genotypes were examined. No significant differences between cases and controls were found correlating the genotypes and the clinical-histopathological parameters. In conclusion, in our population only GSTP1 was associated with breast cancer risk. However, when the genes were tested in combination, a significant association in the breast cancer risk was observed.     

P21 codon 31 polymorphism associated with cancer among white people: evidence from a meta-analysis involving 78,074 subjects

p21 protein is a cell cycle regulator that induces G1 arrest, leading to DNA repair or apoptosis. Previous studies have shown that p21 polymorphism in codon 31 (Ser 31 Arg) may play a role in susceptibility to cancer. However, the results from the published studies are conflicting. To derive a more precise estimation of association between the p21 Ser31Arg polymorphism and risk of cancer, we performed a meta-analysis of 33?120 cancer cases and 44?954 controls from 49 publications with 66 individual case-control studies for the polymorphism. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, no significant association was found between p21 Ser31Arg polymorphism and cancer risk. However, in the subgroup analysis by ethnicity, a significantly elevated risk was found among whites (for Arg/Arg versus Ser/Ser: OR = 1.48, 95% CI = 1.20-1.83; for Arg/Arg versus Ser/Arg +Ser/Ser: OR = 1.49, 95% CI = 1.20-1.83). Interestingly, when stratifying by cancer types, significantly increased risks were observed for breast cancer and 'other cancers' among whites and significantly decreased risks were found for oesophageal cancer and gastric cancer among Asians. When stratifying by sample size of studies, a significantly elevated risk was found among large sample studies (>500 subjects) but not among small sample studies (≤500 subjects). Moreover, a significantly increased risk was observed among smokers in all models except for homozygotes comparison. This meta-analysis suggests that the p21 31Arg allele is a low-penetrant risk factor for cancer development, especially among whites.     

TP53基因多态与结直肠癌肝转移遗传易感性的相关性

目的 探讨TP53基因C-8343G、C-1863T及第72密码子(R72P)单核苷酸多态性与结直肠癌(colorectal cancer,CRC)肝转移风险的关系.方法 采用TaqMan和聚合酶链反应-限制性片段长度多态性方法,检测121例伴肝转移CRC与性别、年龄匹配的280例不伴肝转移CRC的各单核苷酸多态性的基因型分布及差异.结果 C-8343G和C-1863T基因型分布在伴和不伴肝转移的两组CRC人群间差异均无统计学意义.R72P增加CRC肝转移的发生风险:与PP基因型相比,RP基因型、RR基因型和R等位基因携带者(RP或RR基因型)的肝转移风险分别增加至2.21倍(95%CI:1.13～4.33)、2.26倍(95%CI:1.03～4.94)和2.22倍(95%CI:1.16～4.26).CRC组织中P53表达状态的分层分析结果显示:对于P53表达阳性者,72R携带者的肝转移风险与PP基因型相比进一步增加至3.28倍(95%CI:1.21～8.88);而对于P53表达阴性者,PP基因型与72R携带者的肝转移风险差异无统计学意义(比值比为1.37,95%CI:0.52～3.62).结论 TP53增加CRC,特别是P53表达阳性CRC的肝转移风险,可作为CRC肝转移高危人群的筛选指标;C-8343G和C-1863T可能均与CRC肝转移风险无关.