title: Do CDKN2 p16 540 C>G, CDKN2 p16 580 C>T, and MDM2 SNP309 T>G gene variants act on colorectal cancer development or progression?
abstract: CDNK2 p16 plays a pivotal role in G1/S transition by regulating the p53 pathway, which was regulated by a nuclear oncoprotein, mouse double minute 2 (MDM2). Overexpression of the MDM2 gene has been shown in a number of tumor types, its gene amplification is found to associate with accelerated tumor development and failure to treatment in both hereditary and sporadic cancers. Although genetic association studies have revealed the relationship between certain genetic polymorphisms and genes that play important roles in the development and progression of colorectal cancer (CRC), it is still unknown. Therefore, the polymorphisms of p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G designed to investigate the risk of CRC development and progression in a Turkish population. We enrolled 87 patients with CRC and 75 healthy controls into the study. Genotypings were determined using polymerase chain reaction-restriction fragment length polymorphism techniques. Genotype distributions of p16 540 C>G and 580 C>T were found in agreement with the Hardy-Weinberg equilibrium in patients and controls. MDM2 SNP309 T>G was found in agreement with the Hardy-Weinberg equilibrium in controls, but not in patients. The results of our study, the G allele of p16 540 C>G and GG genotype of MDM2 SNP309 T>G were found significantly lower in patients compared with controls (p<0.001, p<0.05, respectively). Haplotype analyses have shown that the C allele of both the CDKN2 p16 540 C>G and 580 C>T variants together indicate a risk haplotype for the patient group; besides, carrying the G allele of p16 540 and G allele of MDM2 also seems a risk haplotype for the patient group. Our study is the first study that investigates the relationship among variants of CDKN2 p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G risk of CRC and the development and progression in the Turkish population.
authors.affiliation: Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Gülay
authors.initials: G
authors.lastname: Tuna
authors.forename: Ozlem
authors.initials: O
authors.lastname: Küçükhüseyin
authors.forename: Soykan
authors.initials: S
authors.lastname: Arıkan
authors.forename: Esra
authors.initials: E
authors.lastname: Kaytan Sağlam
authors.forename: Erkan
authors.initials: E
authors.lastname: Güler
authors.forename: Canan
authors.initials: C
authors.lastname: Cacına
authors.forename: Ozge
authors.initials: O
authors.lastname: Oztop
authors.forename: Saime
authors.initials: S
authors.lastname: Turan
authors.forename: Gurbet
authors.initials: G
authors.lastname: Korkmaz
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylım
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D019942:Genes, p16; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012306:Risk
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2