Background
Racial/ethnic minority groups have a higher burden of renal cell carcinoma (RCC), but RCC among Hispanic Americans (HAs) and American Indians and Alaska Natives (AIs/ANs) are clinically not well characterized. We explored variations in age at diagnosis and frequencies of RCC histologic subtypes across racial/ethnic groups and Hispanic subgroups using National Cancer Database (NCDB) and Arizona Cancer Registry Data.
Methods
Adult RCC cases with known race/ethnicity were included. Logistic regression analysis was performed to estimate odds and 95% confidence interval (CI) of early‐onset (age at diagnosis <50 years) and diagnosis with clear cell RCC (ccRCC) or papillary RCC.
Results
A total of 405 073 RCC cases from NCDB and 9751 cases from ACR were identified and included. In both datasets, patients from racial/ethnic minority groups had a younger age at diagnosis than non‐Hispanic White (NHW) patients. In the NCDB, AIs/ANs had twofold increased odds (OR, 2.21; 95% CI, 1.88‐2.59) of early‐onset RCC compared with NHWs. HAs also had twofold increased odds of early‐onset RCC (OR, 2.14; 95% CI, 1.79‐2.55) in the ACR. In NCDB, ccRCC was more prevalent in AIs (86.3%) and Mexican Americans (83.5%) than NHWs (72.5%). AIs/ANs had twofold increased odds of diagnosis with ccRCC (OR, 2.18; 95% CI, 1.85‐2.58) in the NCDB, but the association was stronger in the ACR (OR, 2.83; 95% CI, 2.08‐3.85). Similarly, Mexican Americans had significantly increased odds of diagnosis with ccRCC (OR, 2.00; 95% CI, 1.78‐2.23) in the NCDB.
Conclusions
This study reports younger age at diagnosis and higher frequencies of ccRCC histologic subtype in AIs/ANs and Hispanic subgroups. These variations across racial/ethnic groups and Hispanic subgroups may have potential clinical implications.
◥Fluorouracil (5-FU) remains a first-line chemotherapeutic agent for colorectal cancer. However, a subset of colorectal cancer patients who have defective mismatch-repair (dMMR) pathway show resistance to 5-FU. Here, we demonstrate that the efficacy of 5-FU in dMMR colorectal cancer cells is largely dependent on the DNA base excision repair (BER) pathway. Downregulation of APE1, a key enzyme in the BER pathway, decreases IC 50 of 5-FU in dMMR colorectal cancer cells by 10-fold. Furthermore, we discover that the facilitates chromatin transcription (FACT) complex facilitates 5-FU repair in DNA via promoting the recruitment and acetylation of APE1 (AcAPE1) to damage sites in chromatin. Downregulation of FACT affects 5-FU damage repair in DNA and sensitizes dMMR colorectal cancer cells to 5-FU. Targeting the FACT complex with curaxins, a class of small molecules, significantly improves the 5-FU efficacy in dMMR colorectal cancer in vitro ($50-fold decrease in IC 50 ) and in vivo xenograft models. We show that primary tumor tissues of colorectal cancer patients have higher FACT and AcAPE1 levels compared with adjacent nontumor tissues. Additionally, there is a strong clinical correlation of FACT and AcAPE1 levels with colorectal cancer patients' response to chemotherapy. Together, our study demonstrates that targeting FACT with curaxins is a promising strategy to overcome 5-FU resistance in dMMR colorectal cancer patients.
RARP is technically feasible for treating localized prostate cancer in RTRs. Graft function did not deteriorate in any patient. Modifications to the standard technique should be considered specifically for port placement, development of the space of Retzius, and performance of lymphadenectomy. Oncologic outcomes remain difficult to interpret given the small number of reported cases.
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