Association of the p53 Codon 72 Polymorphism with Colorectal Cancer in South West of Iran

The p53 tumor suppressor gene plays two important roles in genomic stability: blocking cell proliferation after DNA damage until it has been repaired, and starting apoptosis if the damage is too critical. Codon 72 exon4 polymorphism (Arg72Pro) of the P53 gene has been implicated in cancer risk. Various studies have been done to investigate the status of p53 at codon 72 for arginine (Arg) and proline (Pro) alleles in different populations and also the association of this codon 72 polymorphism with various tumors. Our objective was to investigate the possible association between P53 Arg72Pro polymorphism and susceptibility to colorectal cancer among Isfahan and Chaharmahal Va Bakhtiari (a part of south west of Iran) population. We investigated the status of p53 at codon 72 for Arg/Arg, Arg/Pro and Pro/Pro allele polymorphisms in blood samples from 145 colorectal cancer patients and 140 controls by Nested-PCR of p53 exon 4 and digestion with BstUI restriction enzyme and the DNA fragments were then resolved by electrophoresis in 2% agarose gel. The Pro allele was 279 bp, while the Arg allele was restricted into two fragments of 160 and 119 bp. Among the 145 colorectal cancer cases 49 cases (33.79%) were homozygous for the Arg72 allele (Arg/Arg), 18 cases (12.41%) were homozygous for the Pro72 allele (Pro/Pro) and 78 cases (53.8%) found in heterozygous (Arg/Pro). In conclusion, it can be said that p53Arg/Arg genotype may be correlated with possible increased risk of this kind of cancers in south west of Iran.

Authors:

• A. Doosti
• P. Ghasemi Dehkordi
• M. Zamani
• S. Taheri
• M. Banitalebi
• M. Mahmoudzadeh

Keywords:

• TP53
• Polymorphism
• Colorectal Cancer
• Iran

References:

[1] Z. Z. Zhu, A. Z. Wang, H. R. Jia, X. X. Jin, X. L. He, L. F. Hou, and G.
Zhu, "Association of the TP53 Codon 72 Polymorphism with Colorectal
Cancer in a Chinese Population." Jpn. J. Clin. Oncol., vol. 37, no. 5, pp.
385-390, Nov. 2007.
[2] R. J. C. Steele, "Modern challenges in colorectal cancer." Sorgen, vol. 4,
no. 5, pp. 285-291, Mar. 2006.
[3] R. Gryfe, B. Bapat, S. Gallinger, C. Swallow, M. Redston, and J.
Couture, "Molecular biology of colorectal cancer." Curr. Prob. in
Cancer, vol. 21, no. 5, pp. 233-299, Aug. 1997.
[4] R. Schneider-Stock, C. Boltze, B. Peters, R. Szibor, O. Landt, F. Meyer,
and A. Roessner, "Selective Loss of Codon 72 Proline p53 and Frequent
Mutational Inactivation of the Retained Arginine Allele in Colorectal
Cancer." Neoplasia, vol. 6, no. 5, pp. 529-535, Feb. 2004.
[5] R. Fan, M. T. Wu, D. Miller, J. C. Wain, K. T. Kelsey, J. K. Wiencke,
and D. C. Christiani, "The p53 codon 72 polymorphism and lung cancer
risk." Cancer Epidemiol. Biomark. & Preven., vol. 9: pp. 1037-1042,
Nov. 2000.
[6] M. Oren, "Regulation of the p53 Tumor Suppressor Protein." The J. of
Biologic. Chem., vol. 274, no. 51, pp. 36031-36034, Mar. 1999.
[7] F. W. Lung, T. M. Lee, B. C. Shu, and F. H. Chang, "p53 codon 72
polymorphism and susceptibility malignancy of colorectal cancer in
Taiwan." J. Cancer Res. Clin. Oncol., vol. 130, pp. 728-732. Jan. 2004.
[8] R. Soong, B. Powell, H. Elsaleh, G. Gnanasampanthan, D. R. Smith, H.
S. Goh, D. Joseph, and B. Iacopetta, "Prognostic signicance of TP53
gene mutation in 995 cases of colorectal carcinoma: influence of tumour
site, stage, adjuvant chemotherapy and type of mutation." Europ. J. of
Cancer, vol. 36, pp. 2053-2060, Des. 2000.
[9] A. Langerod, I. R. K. Bukholm, A. Bregard, P. E. Lonning, T. I.
Andersen, T. O. Rognum, G. I. Meling, R. A. Lothe, and A. L. Borresen-
Dale, "The TP53 codon 72 polymorphism may affect the function of
TP53 mutations in breast carcinomas but not in colorectal carcinomas."
Cancer Epidemiol. Biomarkers & Preven., vol. 11, pp. 1684-1688, Mar.
2002.
[10] S. Ara, P. S. Lee, and M. F. Hansen, "Codon 72 polymorphism of the
TP53 gene." Nucleic Acids Res., vol. 18, pp. 4961-4965, Jul. 1990.
[11] A. V. Khrunin, L. A. Tarskaia, V. A. Spitsyn, O. I. Lylova, N. A.
Bebyakova, A. I. Mikulich, and S. A. Limborska, "p53 polymorphisms
in Russia and Belarus: correlation of the 2-1-1 haplotype frequency with
longitude." Mol. Gen. Genomics, vol. 272, pp. 666-672, Feb. 2005.
[12] E. Mammano, C. Belluco, M. Bonafe, F. Olivieri, E. Mugianesi, C.
Barbi, M. Mishto, M. Cosci, C. Franceschi, M. Lise, and D. Nitti,
"Association of p53 polymorphisms and colorectal cancer: Modulation
of risk and progression." EJSO, vol. 35, no. 4, pp. 415-419, Jan. 2009.
[13] S. T. Onrat, E. Ellidokuz, A. Kupelioglu, and E. Durhan, "Frequency of
TP53 codon72 polymorphism in cases with colon cancer." Turk. J. of
Cancer, vol. 39, no. 1, pp. 5-10, Apr. 2009.
[14] L. O. Perez, M. C. Abba, F. N. Dulout, and C. D. Golijow, Evaluation of
p53 codon 72 polymorphism in adenocarcinomas of the colon and
rectum in La Plata, Argentina." World J. Gastroenterol., vol. 12, no. 9,
pp. 1426-1429, Nov. 2006.
[15] N. Sayhan, H. Yazici, M. Budak, O. Bitisik, and N. Dalay, "P53 codon
72 genotypes in colon cancer. Association with human papillomavirus
infection." Res. Commun. Mol. Pathol. Pharmacol., vol. 109: pp. 25-34,
Jul. 2001.
[16] Z. Mojtahedi, M. R. Haghshenas, S. V. Hosseini, M. J. Fattahi, and A.
Ghaderi, "p53 codon 72 polymorphism in stomach and colorectal
adenocarcinomas in Iranian patients." Ind. J. of Cancer., vol. 47, no. 1,
pp. 31-34, Mar. 2010.
[17] M. Nikbahkt Dastjerdi, M. Salehi, M. R. Mohajeri, F. Morsali, H.
Mirmohammad Sadeghi, and E. Esfandiary, "Evidence for an association
of TP53 codon 72 polymorphism with sporadic colorectal cancer risk in
Isfahan." JRMS, vol. 13, no. 6, pp. 317-323, Nov. 2008.
[18] M. Pignatelli, G. W. Stamp, G. Kafiri, D. Lane, and W. F. Bodmer,
"Over-expression of p53 nuclear oncoprotein in colorectal adenomas."
Int. J. Cancer, vol. 50, pp. 683-688, Des. 1992.
[19] B. Khadang, M. J. Fattahi, A. Talei, A. S. Dehaghani, and A. Ghaderi,
"Polymorphism of TP53 codon 72 showed no association with breast
cancer in Iranian women." Cancer Genet. Cytogenet., vol. 173, pp. 38-
42, Jan. 2007.