RESUMO
The germline polymorphisms in signal-inducing proliferation-associated protein 1 (SIPA1) and ribosomal RNR processing 1B (RRP1B) might be involved in breast cancer metastasis. The aim of this study was to analyze how SIPA1 and RRP1B polymorphisms contribute to breast cancer phenotype, lymph node status and survival. A group of 100 young, I-II stage breast cancer patients were analyzed for SIPA1 and RRP1B polymorphisms with PCR-RFLP assay. SIPA1 c.2760G > A, c.545C > T and RRP1B c.436T > C polymorphisms were associated with lymph node status, survival and tumor grade, respectively. Our results suggest that SIPA1 and RRP1B germline polymorphisms are important for breast cancer prognosis.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Ativadoras de GTPase/genética , Mutação em Linhagem Germinativa , Metástase Linfática/genética , Proteínas Nucleares/genética , Polimorfismo Genético , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Lituânia , Pessoa de Meia-Idade , Fenótipo , Análise de SobrevidaRESUMO
BACKGROUND: There is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. However, there is a lack of information on how this epigenetic process differs in tumors originating at different sites in the stomach. The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites. METHODS: Samples were acquired from 81 patients suffering stomach adenocarcinoma who underwent surgery for gastric cancer in the Lithuanian University of Health Sciences Hospital Kaunas Clinics in 2009-2012. Gene methylation was investigated with methylation-specific PCR. The study was approved by the Lithuanian Biomedical Research Ethics Committee. RESULTS: The frequencies of methylation in cancerous tissues from the upper, middle, and lower thirds of the stomach were 11.1, 23.1, and 45.4%, respectively, for MLH1; 22.2, 30.8, and 57.6%, respectively, for MGMT; and 44.4, 48.7, and 51.5%, respectively, for DAPK-1. MLH1 and MGMT methylation was observed more often in the lower third of the stomach than in the upper third (p < 0.05). In the middle third, DAPK-1 promoter methylation was related to more-advanced disease in the lymph nodes (N2-3 compared with N0-1 [p = 0.02]) and advanced tumor stage (stage III rather than stages I-II [p = 0.05]). MLH1 and MGMT methylation correlated inversely when the tumor was located in the lower third of the stomach (coefficient, -0.48; p = 0.01). DAPK-1 and MLH1 methylation correlated inversely in tumors in the middle-third of the stomach (coefficient, -0.41; p = 0.01). CONCLUSION: Gene promoter methylation depends on the gastric tumor location.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Estômago/patologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Interleukin-10 and tumor necrosis factor α play an important role in breast carcinogenesis. Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription. This study analyzes single nucleotide polymorphisms in interleukin 10 and tumor necrosis factor α genes and their contribution to breast cancer phenotype, lymph node status and survival in a group of young Lithuanian women with early-stage breast cancer patients. RESULTS: We genotyped 100 premenopausal Eastern European (Lithuanian) patients with stage I-II breast cancer, ≤ 50 years old at the time of diagnosis, for interleukin 10 -592A > C, -819C > T and -1082A > G and tumor necrosis factor α -308G > A single nucleotide polymorphisms in the gene promoter region. We used the polymerase chain reaction, namely a restriction fragment length polymorphism method, for a SNP analysis. All genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the HapMap CEU population. Holders of IL10 -592A > C heterozygous IL10 -592 AC genotype had a higher probability of estrogen receptor positive breast cancer phenotype than homozygous variants (P = 0.017). Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017). Of all the tested single nucleotide polymorphisms, only TNFα -308G > A has revealed a prognostic capability for breast cancer survival. GA genotype carriers, compared to GG, showed a significant disadvantage in progression-free survival (P = 0.005, adjusted hazard ratio (HR) = 4.631, 95 % confidence interval (CI) = 1.587 - 13.512), metastasis-free survival (P = 0.010, HR = 4.708, 95 % CI = 1.445 - 15.345) and overall survival (P = 0.037, HR = 4.829, 95 % CI = 1.098 - 21.243). CONCLUSIONS: According to our data, IL10 -1082A > G, -819 T > C, -592A > C polymorphisms and phased haplotypes have not revealed a prognostic value for breast cancer. On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Predisposição Genética para Doença , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Pré-Menopausa , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Feminino , Seguimentos , Frequência do Gene , Genótipo , Haplótipos , Humanos , Estimativa de Kaplan-Meier , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Carga TumoralRESUMO
OBJECTIVE. The assessment of breast cancer survival rates and comparison with those of other countries may help to deepen knowledge among decision makers in the health care system and to improve the inequalities in accessibility to early detection and effective treatment. The aim of this study was to evaluate breast cancer survival rates in Kaunas region, Lithuania, and to compare them with those in the selected European countries. MATERIAL AND METHODS. A retrospective study was carried out using medical records and data gathered from the Lithuanian Cancer Registry. A group of 240 patients with primary breast cancer diagnosed in 2008 in Kaunas region was analyzed. All causes of death were included in the analysis. The closing date of follow-up was September 30, 2010. Survival was determined using the life-table method and the Kaplan-Meier method. Cox proportional hazard models were used to estimate the effects of prognostic risk factors on survival. RESULTS. The median age of the patients was 63 years (range, 28-95). The 1-year and 2-year cumulative survival for breast cancer patients in Kaunas region, Lithuania, was 94.2% and 90.1%, respectively. As expected, the survival of patients with diagnosed advanced disease (stage III and IV) was significantly worse than that of patients with stage I (P<0.001) and II (P=0.003) disease. The screening group (aged 50-69 years) showed better survival in comparison with the group older than 69 years. Age, T4 tumor, and distant metastasis were the prognostic factors significantly associated with an increased relative mortality risk of breast cancer. CONCLUSIONS. Compared to the European survival rates, the 1-year and 2-year survival of patients with breast cancer in Lithuania was found to be similar to most European countries.
