RESUMO
Activated Leukocyte Cell Adhesion Molecules (ALCAM, also called CD166, MEMD) are cell surface immunoglobulins that are considered to be prognostic markers for breast cancer. CD166/ALCAM has gained increasing attention because of its significant association with tumor progression and the metastatic spread of breast cancer. Two polymorphisms have been identified in the CD166/ALCAM gene: 5'UTR C/T (rs6437585) and 3'UTR A/G (rs11559013). We analyzed the genotypes of 1033 individuals with breast cancer, and 1116 controls; odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. The effects and functions of polymorphisms were examined using luciferase gene expression assays and real-time PCR analyses. Our data demonstrated that individuals with the rs6437585 CT + TT genotype had an OR of 1.38 (95% CI, 1.11-1.72) for developing breast cancer, compared to those with the CC genotype. The T allele increased the risk of breast cancer in a dose-dependent manner (P (trend) < 0.001). However, there were no significant differences found between cases and controls at the rs11559013 A/G site. Additional experiments that we performed, which focused on reporter gene expression driven by CD166/ALCAM promoters, demonstrated that the presence of an rs6437585 T allele led to greater transcriptional activity than the rs6437585 C allele. This was consistent with the increased cancer risk that we observed in our case-control analysis.
Assuntos
Antígenos CD/genética , Povo Asiático/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Moléculas de Adesão Celular Neuronais/genética , Proteínas Fetais/genética , Polimorfismo Genético/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/secundário , Estudos de Casos e Controles , China/epidemiologia , DNA de Neoplasias/genética , Feminino , Genótipo , Humanos , Luciferases/metabolismo , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Prognóstico , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Fatores de Risco , Adulto JovemRESUMO
Rare alleles at the HRAS1 variable number of tandem repeats (VNTRs) locus have been implicated in breast cancer risk. Although many studies have showed that rare HRAS1 alleles may be associated with breast cancer risk, this relationship remains controversial. A meta-analysis was conducted to investigate the potential association between rare HRAS1 alleles and breast cancer risk. A database search found a total of 13 studies involving 1926 breast cancer cases and 2800 controls. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to test the strength of association. When all the studies were combined into the meta-analysis, we found that breast cancer cases had a significantly higher frequency of rare alleles (OR = 2.03, 95% CI = 1.34, 3.10). In the subgroup analysis by race, we found that breast cancer cases had a significantly higher frequency of rare alleles (OR = 2.14, 95% CI = 1.37, 3.36) among Caucasians. In the subgroup analysis by study design, we found that breast cancer cases had a significantly higher frequency of rare alleles (OR = 2.47, 95% CI = 1.62, 3.79) among groups with hospital-based controls. In conclusion, this meta-analysis suggested that rare alleles at the HRAS1 VNTRs may contribute to breast cancer susceptibility. More population-based case-control studies were needed especially in Asians in the future.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Repetições Minissatélites/genética , Polimorfismo Genético/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos de Casos e Controles , Feminino , Humanos , Prognóstico , Fatores de RiscoRESUMO
The matrix metalloproteinases (MMP) can degrade various components of the extracellular matrix and its functional genetic polymorphisms may be associated with breast cancer risk. However, this relationship remains controversial. A meta-analysis was conducted in order to investigate the potential association between four polymorphisms in the MMP gene and breast cancer risk. A database search yielded a total of 9 studies involving 2,597 cases and 2,618 controls. Four polymorphisms were included in the meta-analysis: MMP-1 -1607 2G/1G (rs1799750), MMP-2 -1306 C/T (rs243865), MMP-3 -1171 6A/5A (rs3025058) and MMP-9 -1562 C/T (rs3918242). Crude odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, we found that breast cancer cases had a significantly higher frequency of CC genotype (OR = 1.27, 95% CI = 1.10, 1.47; P = 0.001) and lower frequency of CT genotype (OR = 0.78, 95% CI = 0.67, 0.91; P = 0.001) of MMP-2. No significant difference was found in any genotype of MMP-1, MMP-3 or MMP-9. In conclusion, this meta-analysis suggested that MMP-2 -1306 C/T polymorphism may contribute to breast cancer susceptibility. More studies were needed especially in Asians in the future.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Metaloproteinases da Matriz/genética , Polimorfismo de Nucleotídeo Único , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Razão de Chances , Regiões Promotoras Genéticas , RiscoRESUMO
OBJECTIVE: The aim of this meta-analysis is to evaluate associations between LTA-252 A>G and breast cancer (BC). METHODS: Electronic searches of several databases were conducted for all online publications. A total of 7 studies involving 4,625 BC patients and 4,373 controls were identified. RESULTS: This meta-analysis showed no significant association between the LTA-252 A>G polymorphism and BC in overall or Caucasian populations. However, a positive association was found limited to Asian populations. CONCLUSION: Although there was no significant association found between the LTA-252 A>G polymorphism and BC overall, a positive association was found in Asian populations.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Linfotoxina-alfa/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Feminino , Humanos , PrognósticoRESUMO
BACKGROUND AND OBJECTIVES: Tumor necrosis factor-α (TNF-α) plays a very important role in the development and progress of cancer. Some TNF-α polymorphisms have been confirmed to increase cancer risks; however, the association between TNF-α-238 polymorphism and cancers remains controversial and ambiguous. The aim of this study is to explore a more precise estimation of its relationship with cancer using meta-analysis. METHODS: Electronic searches of several databases were conducted for all publications on the association between this variant and cancer through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association in the random-effect model. RESULTS: Thirty four studies with 34,679 cancer patients and 41,186 healthy controls were included. This meta-analysis showed no significant association between TNF-α-238 polymorphism and cancers (AA+GA vs GG: ORâ=â1.09, 95%CIâ=â0.88-1.34). In Caucasian and Asian subgroups, OR values (95% CI) were 1.14 (0.91-1.43) and 0.97 (0.58-1.61), respectively. In the subgroups of cancer type, no significant association was detected. The sensitivity analysis further strengthened the validity of these negative associations. No publication bias was observed in this study. CONCLUSIONS: No significant association was found between the TNF-α-238 polymorphism and the risk for cancer.