Alterations of cell kinetics in familial adenomatous polyposis and sporadic colorectal adenoma and carcinoma

Abstract

History Library). 7 kindreds were identified as non-FAP, non-HNPCC FCRC (1-2 index CRC cases from each kindred tested negative for germline mutations in the APC, MSH2, and MLHI genes; and/or microsatellite instability). Colonoscopies were performed in 10(degree), 2°, and 3° relatives (rei) of CRC cases from the 7 kindreds. Results: In the entire UPDB, the ave. age of CRC dx was not significantly different between kindreds with a rei risk for CRC >2 or <2. There were 15 index patients with FCRC (ave. age of diagnosis(dx)= 58(41-72)y/o): 8 in females (ave. age of dx = 56 (41-72) y/o; 3 in right colon (RC) and 5 in left colon (LC» and 7 in males (ave. age of dx = 61 (46-69) y/o; 7 in RC and 8 in LC). 159 relatives of the 15 index CRC cases underwent 201 colonoscopies (only initial colonoscopy data was evaluated): (see Table I) Adenomas were found in 18 males (*30% in RC and 70% in LC) and 32 females (*65.8% in RC and 34.2% in LC)(*p=.03). In 1° rei, 28/57 (50%t)adenomas were in the RC, and in the 2° and 3° deg rei, 14/40 (35%t) were in the RC (tp=.2). Adenomas with high-grade dysplasia were found in the RC in 3 females (I had synchronous CRC and 2 were I ° rei). Conclusions: Age of CRC dx was similar between high and low familialrisk kindreds. In non-FAP, non-HNPCC FCRC: I) More I ° rei of CRC cases expressed adenomatous polyps than similar aged 2° and 3° rei after, but not before age 60. 2) Women and 1° rei, but not 2° and 3° rei, were predisposed to RC adenomas, justifying full colon screening. Unexpectedly, hereditary factors in FCRC appear to increase the risk of neoplasia later in life.