APOBEC3A/B deletion polymorphism and cancer risk.

Activity of the apolipoprotein B mRNA editing enzyme, catalytic-polypeptide-like (APOBEC) enzymes has been linked to specific mutational processes in human cancer genomes. A germline APOBEC3A/B deletion polymorphism is associated with APOBEC-dependent mutational signatures, and the deletion allele has been reported to confer an elevated risk of some cancers in Asian populations, while the results in European populations, so far, have been conflicting. We genotyped the APOBEC3A/B deletion polymorphism in a large population-based sample consisting of 11 106 Caucasian (Norwegian) individuals, including 7279 incident cancer cases (1769 breast, 1360 lung, 1585 colon, and 2565 prostate cancer) and a control group of 3827 matched individuals without cancer (1918 females and 1909 males) from the same population. Overall, the APOBEC3A/B deletion polymorphism was not associated with risk of any of the four cancer types. However, in subgroup analyses stratified by age, we found that the deletion allele was associated with increased risk for lung cancer among individuals <50 years of age (OR 2.17, CI 1.19-3.97), and that the association was gradually reduced with increasing age (P = 0.01). A similar but weaker pattern was observed for prostate cancer. In support of these findings, the APOBEC3A/B deletion was associated with young age at diagnosis among the cancer cases for both cancer forms (lung cancer: P = 0.02; dominant model and prostate cancer: P = 0.03; recessive model). No such associations were observed for breast or colon cancer.

Rectal cancer in the young patient.

PURPOSE: The purpose of this national study was to evaluate the results of treatment for young rectal cancer patients. METHODS: This prospective study from the Norwegian Rectal Cancer Project includes all 2,283 patients younger than aged 70 years with adenocarcinoma of the rectum from November 1993 to December 1999. Patients younger than aged 40 years (n = 45), 40 to 44 years (n = 87), 45 to 49 years (n = 153), and 50 to 69 years (n = 1998) were compared for patient and tumor characteristics and five-year overall survival. Patients treated for cure (n = 1,354) were evaluated for local recurrence, distant metastasis, and disease-free survival. RESULTS: Patients younger than aged 40 years had significantly higher frequencies of poorly differentiated tumors (27 vs. 12-16 percent; P = 0.014), N2-stage (37 vs. 13-18 percent; P = 0.001), and distant metastases (38 vs. 19-24 percent; P = 0.019) compared with older patients. Among those treated for cure, 56 percent of the patients younger than aged 40 years developed distant metastases compared with 20 to 26 percent of the older patients (P = 0.003). Overall five-year survival was 54 percent for patients younger than aged 40 years compared with 71 to 88 percent for the older patients (P = 0.029). Age younger than 40 years was a significant independent prognostic factor and increased the risk for metastasis and death. CONCLUSIONS: Patients younger than aged 40 years had a more advanced stage at the time of diagnosis and poor prognosis compared with older patients. Young patients treated for cure more often developed distant metastases and had inferior survival.

Transanal excision vs. major surgery for T1 rectal cancer.

PURPOSE: The purpose of this national study was to examine the long-term results of transanal excision compared with major surgery of T1 rectal cancer. METHODS: This prospective study from the Norwegian Rectal Cancer Project included all 291 patients with a T1M0 tumor within 15 cm from the anal verge treated by anterior resection, abdominoperineal resection, Hartmann's procedure, or transanal excision in the period from November 1993 to December 1999. RESULTS: Two hundred fifty-six patients were treated by major surgery and 35 patients by transanal excision. None of the patients had neoadjuvant therapy. Macroscopic tumor remnants (R2) occurred in 17 percent (6/35) of the transanal excisions, while major surgery obtained 100 percent R0 resections. Eleven percent of the patients treated with major surgery had glandular involvement. There were no significant differences according to tumor localization, size, or differentiation between Stage I and Stage III tumors. Patients treated with transanal excision were older than patients having major surgery (mean age, 77 vs. 68 years, P < 0.001). After curative resection (R0, R1, Rx) the five-year rate of local recurrence was 12 percent (95 percent confidence interval, 0-24) in the transanal excision group compared with 6 percent (95 percent confidence interval, 2-10) after major surgery (P = 0.010). The overall five-year survival was 70 percent (95 percent confidence interval, 52-88) in the transanal excision group compared with 80 percent (95 percent confidence interval, 74-85) in the major surgery group (P = 0.04) and the five-year disease-free survival was 64 percent (95 percent confidence interval, 46-82) in the transanal excision group compared with 77 percent (95 percent confidence interval, 71-83) in the major surgery group (P = 0.01). CONCLUSIONS: The main problem of transanal excision for early rectal cancer in the present study was the inability to remove all the malignancy. Patients treated with transanal excision had significantly higher rates of local recurrence compared with patients who underwent major surgery. Patients who had transanal excision had inferior survival, but they were older than those who had major surgery.