Increased risk of colorectal adenomas in Italian subjects carrying the p53 PIN3 A2-Pro72 haplotype.
BACKGROUND
Few reports have investigated the association of two p53 polymorphisms (Arg72Pro and PIN3-A2) with colorectal cancer (CRC) risk, and no previous study has analyzed their role as susceptibility alleles for colorectal adenoma.


OBJECTIVE
To explore the impact of the p53 PIN3-Arg72Pro haplotype on colorectal adenoma formation and progression to cancer.


METHODS
One hundred and eighty-four colorectal tumor patients (124 with adenomas and 60 with adenocarcinoma) and 188 controls (42 subjects with a clean colon, 54 hospital controls and 92 blood donors) from the Italian population were tested for PIN3-Arg72Pro haplotype status.


RESULTS
A significantly increased risk of colorectal adenomas was observed in patients carrying the PIN3 A2-Pro72 haplotype (OR = 2.02, 95% CI: 1.17-3.48; p = 0.01), while those carrying the PIN3 A1-Pro72 haplotype had a significantly increased risk of developing CRC (OR = 3.33; 95% CI: 1.40-7.89; p = 0.006). Comparisons of cases with the clean colon control group provided stronger evidence of the associations. A family history of CRC did not affect the risk estimates. No association was observed between the pathologic features of adenomas, the Arg72Pro and PIN3 polymorphisms, and the PIN3-Arg72Pro haplotype.


CONCLUSIONS
Our finding that two different p53 haplotypes are associated with colorectal adenoma and cancer, respectively, suggests that each of these haplotypes may independently impact on p53 function(s) within different genetic pathways of colorectal carcinogenesis.
Perfumo
Chiara
C
Unit of Molecular Mutagenesis, National Institute for Cancer Research, Genoa, Italy. chiara.perfumo@istge.it
Bonelli
Luigina
L
Menichini
Paola
P
Inga
Alberto
A
Gismondi
Viviana
V
Ciferri
Enrico
E
Percivale
Pierluigi
P
Bianchi Scarrà
Giovanna
G
Nasti
Sabina
S
Fronza
Gilberto
G
Varesco
Liliana
L
D000236:Adenoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution