Published online May 7, 2016. doi: 10.3748/wjg.v22.i17.4380
Peer-review started: December 7, 2015
First decision: January 28, 2016
Revised: February 2, 2016
Accepted: March 2, 2016
Article in press: March 2, 2016
Published online: May 7, 2016
AIM: To identify prognostic factors and to correlate APC mutations with clinical features, including extracolic manifestations.
METHODS: One hundred thirty-five patients who underwent surgical procedures for familial adenomatous polyposis (FAP) were included. FAP was diagnosed when the number of adenomatous polyps was > 100. Data related to patient, extracoloic manifestations, cancer characteristics, operative procedure, follow up and surveillance were collected. APC mutation testing was performed in the 30 most recent patients. DNA was extracted from peripheral blood and polymerase chain reaction products using 31 primer pairs on APC gene were sequenced. A retrospective study was performed to investigate a causal relationship between prognosis and feature of patient.
RESULTS: The mean age of the 51 patients with colorectal cancer (CRC) was older than that of those without CRC (30.5 vs 36.9, P = 0.002). Older individuals were more likely to have colon cancer at the time of FAP diagnosis [odds ratio, 4.75 (95%CI: 1.71-13.89) and 5.91(1.76-22.12) for 40-49 years and age > 50 vs age < 30). The number of confirmed deaths was 13 and the median age at death was 40 years (range, 27 to 85 years). Ten of the deaths (76.9%) were from CRC. Another cause of two cases of death were desmoid tumors (15.4%). Development of cancer on remnant rectal or ileal mucosa after surgery was not observed. The APC mutation testing revealed 23 pathogenic mutations and one likely pathogenic mutation, among which were four novel mutations. The correlation between mutational status and clinical manifestations was investigated. Mutations that could prodict poor prognosis were at codon 1309 which located on mutation cluster region, codon 1465 and codon 1507.
CONCLUSION: Identification of APC mutations should aid in the diagnosis and counseling of family members in terms of early diagnosis and management of FAP.
Core tip: Diagnostic delay to make adequate management harder, resulting in advanced colorectal cancer and accompanying morbidities, was not uncommon in patients with familial adenomatous polyposis. This study investigated prognostic factors and the correlation between APC mutations and clinical features, including extracolic manifestations. The present study revealed that early diagnosis and management of high-risk patients is essential and suggests the necessary APC mutations testing in the diagnosis and counseling of patients by informing on disease prognosis.