Microsatellite instability and aneuploidy rate in young colorectal-cancer patients do not differ significantly from those in older patients

DNA and chromosomal instabilities are thought to promote colorectal carcino genesis. Mismatch repair (MMR) deficiency affects DNA-sequence integrity, r esulting in microsatellite instability (MI), Tumor aneuploidy (AN) has been shown to reflect underlying chromosomal instability (CI), This study aimed at assessing the MI and AN rate of Singapore's colorectal-cancer (CRC) pat ients, who are predominantly Chinese, in association with age group, tumor site, Dukes' staging and gender. In contrast to a Caucasian series, the MI rate for our younger patients aged 40 or less without family history (23%) is not significantly different from that for older, sporadic patients (13%) aged 60 or more, suggesting that population screening for germline MMR mut ations is unlikely to be cost-effective. Our MI-positive patients also show no significant differences from the MI-negative patients with respect to t umor site, staging, ploidy status and gender. This implies that the local M I-positive individuals may have a different profile from that of the Caucas ians, indicating the possibility of underlying genetic differences. AN is a lso not significantly more prevalent in younger patients, In addition, a si gnificant 21% of our patients (p < 0.00005) show no evidence of either the MI or CI pathways, implying that there is at least a third pathway driving colorectal carcinogenesis, involving neither genes that maintain DNA sequen ce stability nor genes that cause guess chromosomal segregation defects. In t. J. Cancer 80:667-670, 1999. (C) 1999 Wiley-Liss, Inc.