title: TP53 Arg 72Pro and MDM2 SNP309 polymorphisms and colorectal cancer risk: a west Algerian population study.
abstract: The tumor suppressor gene TP53 and its regulator MDM2 are both key players involved in multiple pathways including apoptosis, cellular transcriptional control and cell cycle regulation. Common germline polymorphisms in these genes may affect colorectal cancer (CRC) susceptibility. An arginine-to-proline substitution at codon 72 in the TP53 gene is reported to decrease apoptotic potential, while a thymine-to-guanine polymorphism at nucleotide 309 (named SNP309) of murine double minute 2 MDM2 gene increases its transcription. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer in the Algerian population was addressed in this study. DNA samples from 121 controls and 116 cases were genotyped for these two polymorphisms by PCR/RFLP then confirmed by sequencing. Unexpectedly no significant association was found between this potential marker TP53 Arg72Pro and CRC (p > 0.05). However, our findings reveal that individuals with the MDM2 SNP309 GG genotype have a low risk of CRC as compared to the TT genotype (OR = 0.49; 95 % CI: 0.24-0.98, p = 0.04), with more significance for females (OR = 0.16; 95 % CI: 0.06-0.41, p < 0.05). Moreover, no significant association was observed between the combined TP53 and MDM2 genotypes and CRC. Contrary to initial expectations that the GG genotype with high MDM2 levels would increase cancer risk, our results demonstrate that the MDM2 SNP309 GG genotype is associated with decreased risk of colorectal cancer. This is suggesting that other mechanisms independent of increased MDM2 levels can influence cancer susceptibility.
authors.affiliation: Laboratoire de Génétique Moléculaire et Cellulaire, Département de Génétique Moléculaire Appliquée, Faculté des sciences de la nature et de la vie, Université des Sciences et de la Technologie d'Oran- Mohamed BOUDIAF-USTOMB, BP 1505 El M'naouer, 31000, Oran, Algeria, abderrahmane_rym@yahoo.fr.
authors.forename: Rym
authors.initials: R
authors.lastname: Abderrahmane
authors.forename: Lotfi
authors.initials: L
authors.lastname: Louhibi
authors.forename: Fatima Zohra
authors.initials: FZ
authors.lastname: Moghtit
authors.forename: Amina
authors.initials: A
authors.lastname: Boubekeur
authors.forename: Khedidja
authors.initials: K
authors.lastname: Benseddik
authors.forename: Abdellah
authors.initials: A
authors.lastname: Boudjema
authors.forename: Fouzia
authors.initials: F
authors.lastname: Benrrahal
authors.forename: Meriem
authors.initials: M
authors.lastname: Aberkane
authors.forename: Mostefa
authors.initials: M
authors.lastname: Fodil
authors.forename: Nadhira
authors.initials: N
authors.lastname: Saidi-Mehtar
mesh_terms: D000462:Algeria / Q000453:epidemiology; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012007:Rectum / Q000378:metabolism; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2