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Carcinogenesis Advance Access originally published online on October 14, 2004
Carcinogenesis 2005 26(1):103-107; doi:10.1093/carcin/bgh305
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Carcinogenesis vol.26 no.1 © Oxford University Press 2005; all rights reserved.

ARTICLE

Polymorphism of the p73 gene in relation to colorectal cancer risk and survival

Daniella Pfeifer1, Gunnar Arbman2 and Xiao-Feng Sun1,3

1 Department of Oncology, Institute of Biomedicine and Surgery, University of Linköping, Linköping, Sweden and 2 Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden

3 To whom correspondence should be addressed Email: xiasu{at}ibk.liu.se

The results regarding a GC/AT polymorphism in the p73 gene in relation to cancer risk are inconsistent, and the significance of loss of heterozygosity (LOH) of the gene is unclear. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. 179 patients with colorectal cancer and 260 healthy controls were genotyped for the polymorphism by PCR-restriction fragment length polymorphism (RFLP). Fifty informative cases were examined for LOH in tumours. Immunohistochemistry was performed on distant (n = 42) and adjacent normal mucosa (n = 33), primary tumour (n = 6 9) and lymph node metastasis (n = 12). The frequencies of the genotypes were 63% for wild-type (GC/GC), 30% for heterozygotes (GC/AT) and 7% for variants (AT/AT) in patients, and 62, 36 and 2% in controls, respectively. The frequencies of the genotypes in the patients and controls were significantly different (P = 0.02). The patients carrying the AT allele had a better prognosis than those with the GC/GC genotype (OR = 0.42, 95% CI = 1.15–5.02, P = 0.02). No LOH was observed at the p73 locus. Expression of p73 protein was increased from normal mucosa to primary tumours (P = 0.02), but was not significantly changed between primary tumours and metastases (P = 1.0). In conclusion, the AT/AT homozygotes may have a greater risk of developing colorectal cancer, while the patients who carried the AT allele had a better prognosis.


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