Abstract :
Background: The tumor suppressor gene TP53 (alias p53)
located on chromosome 17 is involved in various cancers.
Case-control studies have shown that p53 codon 72 polymorphism
modulates the prognosis and susceptibility to various
malignancies. We undertook the present study to explore a
possible association between mucinous and non-mucinous
adenocarcinomas with different genotypes or alleles at codon
72 of TP53.
Methods: The genotype distribution and allelic frequencies
for p53 polymorphism was assessed in 46 and 134 specimens
from patients with colorectal mucinous and non-mucinous
adenocarcinomas, respectively, by using allele-specific PCR.
Results: The PCR products were 177bp for proline allele and
141bp for arginine allele. In the mucinous samples, the genotype
distribution for p53 polymorphism showed 63%, 23.9%,
and 13.1% for the Arg/Arg, Arg/Pro, and Pro/Pro genotypes,
respectively. In the non-mucinous specimens 32.1% of the
cases were Arg/Arg, 48.5% Arg/Pro, and 19.4% pro/pro. A significant
difference between the two types of adenocarcinomas
for the Arg 72 Arg genotype compared with (grouped) Arg 72
Arg and Pro 72 Pro genotypes was noted [OR=3.61 (1.76-7.27),
P<0.001]. The arginine allele was found more often in patients
with mucinous adenocarcinoma [OR=1.85 (1.07-3.19), P<0.03].
A higher portion of Dukes stage C was noted in the mucinous
specimens (P<0.02) and also mucinous specimens were seen
more often at advanced TNM stages (P=0.01).
Conclusion: The Arg/Arg genotype at p53 codon 72 is more
prevalent in mucinous colorectal carcinoma and the arginine
allele may contribute to mucinous carcinogenesis. The proline
allele was associated with higher Duke's staging in nonmucinous
adenocarcinoma.
Keywords :
TP53 , polymorphism , colorectal neoplasm , mucinous , adenocarcinoma