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 carcinogenesis. Mismatch repair (MMR) deficiency affects DNA-sequence integrity, resulting 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) patients, 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 mutations is unlikely to be cost-effective. Our MI-positive patients also show no significant differences from the MI-negative patients with respect to tumor site, staging, ploidy status and gender. This implies that the local MI-positive individuals may have a different profile from that of the Caucasians, indicating the possibility of underlying genetic differences. AN is also not significantly more prevalent in younger patients. In addition, a significant 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 sequence stability nor genes that cause gross chromosomal segregation defects.
Department of Colorectal Surgery, Singapore General Hospital, Republic of Singapore.
J
J
Yao
K W
KW
Eu
F
F
Seow-Choen
V
V
Vijayan
P Y
PY
Cheah
D000328:Adult; D000367:Age Factors; D000368:Aged; D000782:Aneuploidy; D016009:Chi-Square Distribution; D002681:China / Q000208:ethnology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D004171:Diploidy; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D012727:Sex Characteristics; D012846:Singapore
D017931:DNA Primers; D004273:DNA, Neoplasm