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Background: DKC1 (dyskerin pseudouridine synthase 1) is a causative gene for X-linked dyskeratosis congenita. Approximately 8% of patients with dyskeratosis congenita have malignancy, but information about the development of malignancy in patients with dyskeratosis congenita is limited.Case Presentation: A young Japanese patient with bone marrow failure developed metachronous rectal adenocarcinomas at the ages of 16 and 18 years. He had no family history of cancer. Microsatellite instability testing with rectal tumor tissue demonstrated low-level microsatellite instability. To clarify whether any cancer susceptibility genes were involved in the development of rectal cancer, RNA sequencing was performed. Cancer-related genes were assessed, and a c.361A>G (p.Ser121Gly) germline variant was detected in DKC1. The same missense variant was previously reported in two patients with dyskeratosis congenita as a pathogenic variant, but those patients did not develop malignancies.Conclusions: Our patient developed rectal cancer at an early age of onset compared with the previously reported typical onset age of patients with dyskeratosis congenita. DKC1 might be involved in predisposition to colorectal cancer in young adulthood; therefore, appropriate surveillance may be considered. [ABSTRACT FROM AUTHOR]

Background: We conducted a randomized phase III trial comparing tegafur/uracil (UFT) and Polysaccharide-K (PSK) to surgery alone in curatively resected stage II rectal cancer patients.Methods: Patients were randomly assigned to receive either UFT and PSK or surgery alone in a 1:1 ratio with a minimization method to balance the treatment allocation. The primary end point of this study was the disease-free survival (DFS). The secondary end point was the overall survival (OS).Results: From October 2011 to February 2013, 111 patients were registered from 62 institutions. The study was prematurely closed due to poor accrual after reaching 20% of its goal. The patients' characteristics were similar between the UFT and PSK group and the surgery-alone group. The DFS rate was 76.0% at 3 years and 65.1% at 5 years in the UFT and PSK arm and 84.0% at 3 years and 77.2% at 5 years in the surgery-alone arm. The DFS was slightly worse in the UFT + PSK arm than in the surgery-alone arm, but the difference did not reach statistical significance (log rank p = 0.102). The OS rate was 100% at 3 years and 97.9% at 5 years in the UFT + PSK arm, while that was 100% at 3 years and 93.4% at 5 years in the surgery-alone arm. The OS was similar in the UFT + PSK arm and surgery-alone arm (p = 0.533).Conclusion: The present study suggests that UFT and PSK are not attractive candidates to advance to the next phase III study because the DFS was slightly worse in the UFT and PSK arm than in the surgery-alone arm. [ABSTRACT FROM AUTHOR]

Background: Although several markers, including the lymph node ratio (LNR), have been proposed as a clinically prognostic tool for colorectal cancer (CRC), it remains unclear which markers have the most relevance in determining recurrence following adjuvant chemotherapy for stage III CRC.Methods: Independent risk factors for recurrence-free survival (RFS) were retrospectively determined using the Cox proportional hazard model in 360 stage III CRC patients and validated using an independent cohort comprising 172 stage III CRC patients.Results: The LNR was independently associated with RFS (HR, 1.96; 95% CI, 1.11 to 3.28; P = 0.020). A higher LNR value was significantly associated with recurrence, microsatellite stable, and shorter time to recurrence. A combination of the LNR with pre-chemotherapy CEA and CA19-9, other independent risk factors, provided accurate risk stratification of RFS and conferred additional information on recurrence within each stage III CRC subgroup, which was then validated in an independent cohort. A beneficial effect in patients at risk of recurrence, and a reduced effect in patients at low risk, was exhibited by the addition of oxaliplatin to 5-fluorouracil-based adjuvant chemotherapy.Conclusion: A higher LNR is one of the most aggressive phenotypes with recurrence risk following adjuvant chemotherapy for stage III CRC. [ABSTRACT FROM AUTHOR]