MUCOSAL POLYAMINE MEASUREMENTS AND COLORECTAL-CANCER RISK

Polyamines are short-chain aliphatic amines required for normal cellul ar growth that are ubiquitously found in all living tissues. Polyamine content has been shown to correlate with cellular proliferation. Quan titation of polyamines may thus provide a biochemical measure of proli feration in the colorectal mucosa where dysregulated epithelial prolif eration is associated with colorectal cancer risk. A case-control stud y was conducted to validate the hypothesized association between mucos al polyamine measurements and colorectal cancer risk. Polyamines were measured in 4-6 multiple rectal mucosal biopsies from 11 normal contro l subjects and seven case patients with colon cancer. Compared with th e controls, mean polyamine measurements, after adjustment for age and sex, were significantly increased for spermidine (P < 0.003) and sperm ine (P < 0.017). Subsequent analyses indicated that in controls 1-4 bi opsies appeared adequate to characterize an individual. However, mucos al polyamines in the cases exhibited more sampling variability, requir ing 4-8 biopsies to achieve an acceptable level of reliability. After adjustment for age and sex, the odds ratios for spermidine and spermin e levels, compared to the controls, were 4.8 (95% confidence interval: 1.6-33.7) and 2.3 (1.2-6.3), respectively. The results of this study indicate that increases of mucosal polyamine measurements, after takin g the sampling and methodological variability into account, are signif icantly associated with colorectal cancer risk, and suggest that polya mine measurements in rectal mucosa may play an important role as bioma rkers for identifying high-risk individuals and/or for using as interm ediate endpoints in prevention trials. (C) 1996 Wiley-Liss, Inc.