RESUMO
BACKGROUND: Obesity constitutes a risk factor for the development of aggressive forms of prostate cancer. It has been proposed, that prostate cancer has a genetic predisposition and that PPARGC1A and ADIPOQ polymorphisms play a role in the development of this condition. OBJECTIVE: To analyse the association of two PPARGC1A and ADIPOQ polymorphisms as well as their haplotypes, with the development of aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity. SUBJECTS AND METHODS: Two hundred fifty seven men with prostate cancer of Mexican-Mestizo origin were included. Body mass index (BMI) was determined and the degree of prostate cancer aggressiveness by the D'Amico classification. DNA was obtained. Rs7665116 and rs2970870 of PPARGC1A, and rs266729 and rs1501299 of ADIPOQ were studied by real-time PCR allelic discrimination. Pairwise linkage disequilibrium, between single nucleotide polymorphisms was calculated and haplotype analysis was performed. RESULTS: A higher-risk (D'Amico classification) was observed in 21.8% of patients. An association of cancer aggressiveness with rs2970870 of PPARGC1A, and rs501299 of ADIPOQ, as well as with one haplotype of ADIPOQ was documented. CONCLUSIONS: This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity.
Assuntos
Adiponectina/genética , Obesidade/genética , Sobrepeso/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Neoplasias da Próstata/genética , Estudos Transversais , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , México , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/etnologia , Sobrepeso/complicações , Sobrepeso/etnologia , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Mitochondrial dysfunction has been associated with the development of cancer and obesity, being prostate cancer more aggressive in obese men. It has been suggested that the mitochondrial transcription factor A (TFAM) plays a central role in these events. OBJECTIVE: The aim of this study was to analyze the possible association of 3 TFAM polymorphisms, as well as their haplotypes, with the development of aggressive prostate cancer in overweight or obese Mexican Mestizo men. SUBJECTS AND METHODS: A total of 257 unrelated men with histologically confirmed prostate cancer, of Mexican Mestizo ethnic origin, were included. Body mass index was determined and the degree of prostate cancer aggressiveness was demarcated by the D'Amico classification. DNA was obtained from blood leukocytes. The rs1937, rs1049432, and rs11006132, as well as their haplotypes, were studied by real-time polymerase chain reaction allelic discrimination. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated; haplotype analysis was performed. RESULTS: A higher risk (D'Amico classification) was documented in 56 patients (21.8%). We did not find a significant association among those polymorphisms analyzed; however, one haplotype was significantly associated with cancer aggressiveness. CONCLUSIONS: To our knowledge, this constitutes the first study regarding the relationship of 3 TFAM polymorphisms, as well as their haplotypes, and the aggressiveness of prostate cancer in overweight or obese men; the most frequent haplotype was associated with cancer aggressiveness.