BACKGROUND:Telomere-related genes play an important role in carcinogenesis and progression of prostate cancer (PCa). It is not fully understood whether genetic variations in telomere-related genes are associated with development and progression in PCa patients. METHODS: Six potentially functional single-nucleotide polymorphisms (SNPs) of three key telomere-related genes were evaluated in 1015 PCa cases and 1052 cancer-free controls, to test their associations with risk of PCa. Among 426 PCa patients who underwent radical prostatectomy (RP), the prognostic significance of the studied SNPs on biochemical recurrence (BCR) was also assessed using the Kaplan-Meier analysis and Cox proportional hazards regression model. The relative telomere lengths (RTLs) were measured in peripheral blood leukocytes using real-time PCR in the RP patients. RESULTS: TEP1 rs1760904 AG/AA genotypes were significantly associated with a decreased risk of PCa (odds ratio (OR): 0.77, 95% confidence interval (CI): 0.64-0.93, P = 0.005) compared with the GG genotype. By using median RTL as a cutoff level, RP patients with TEP1 rs1760904 AG/AA genotypes tended to have a longer RTL than those with the GG genotype (OR: 1.55, 95% CI: 1.04-2.30, P = 0.031). A significant interaction between TEP1 rs1713418 and age in modifying PCa risk was observed (P = 0.005). After adjustment for clinicopathologic risk factors, the presence of heterozygotes or rare homozygotes of TEP1 rs1760904 and TNKS2 rs1539042 were associated with BCR in the RP cohorts (hazard ratio: 0.53, 95% CI: 0.36-0.79, P = 0.002 and hazard ratio: 1.67, 95% CI: 1.07-2.48, P = 0.017, respectively). CONCLUSIONS: These data suggest that genetic variations in the TEP1 gene may be biomarkers for risk of PCa and BCR after RP.
Background: Right-and left-sided colon cancers are considered two distinct entities, with differences in embryological origin, clinical presentation and tumor biology. Although unclear whether these differences have meaningful impact in mortality, right colon location is many times associated with a worse prognosis. Some studies, however, have suggested that right colon location in stage II disease is associated with better overall survival, in contrast with the more advanced stages. The aim of this study is to assess the differences between primary tumor location in terms of disease free survival (DFS) and overall survival (OS). Methods: We identified all patients with AJCC stage II primary adenocarcinoma of the colon diagnosed from 2008 to 2013 in three hospitals in the Greater Lisbon Area, who underwent surgery for curative intent. Disease free survival (DFS) and overall survival (OS) were examined using the Kaplan-Meier survival analysis and Cox proportional hazards regression. Results: Among the 652 patients identified, 49% had right-sided colon cancer (RCC). There was no difference in age or sex demographics between RCC and left-sided colon cancer (LCC). Regarding the high-risk factors, grade 3 tumors were more common in RCC (p-value¼0.040); less than 12 removed lymph nodes and the presence of occlusion were more common in LCC (p-value¼0.005 and p-value¼0.006, respectively). No statistically significant difference was observed between RCC and LCC patients in disease free survival (HR 1.016 95%CI 0.615,1.679, p-value¼0.949) or overall survival (HR 0.980 95%CI 0.588,1.634 p-value¼0.938). Adjusting for sex, age group, chemotherapy and high risk features, there were still no differences observed between RCC and LCC, both in terms of DFS (HR 1.127 95%CI 0.680,1.868,) and OS (HR 1.086 95%CI 0.647, 1.822, p-value¼0.754). Conclusions: These findings demonstrate that, in stage II disease, there was no overall difference in DFS and OS between right-and left-sided colon cancers. Although there has been an increasing interest in determining the prognostic value of sideness in colon cancer, this may be of lesser importance in earlier stages.
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