615 - Single nucleotide polymorphisms (SNPs) in the p53, SMAD7 and TGFBR1 genes associated with advanced colorectal cancer in caucasian patients compared...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Marc Pauly
Authors M. Pauly1, G. Mahon2, M.A. Dicato3, B. Metzger4, A. Menzel5
  • 1Laboratoire De Recherche Sur Le Cancer Et Les Maladies Du Sang, Foundation for Research on Cancer, 1210 - Luxembourg/LU
  • 2Fondation Recherche Sur Le Cancer, Foundation for Research on Cancer, 1210 - Luxembourg/LU
  • 3Hematology- Oncology, Centre Hospitalier de Luxembourg, 1210 - Luxembourg/LU
  • 4Foundation for Research on Cancer, 1210 - Luxembourg/LU
  • 5Biology Moléculaire, Laboratoires Réunis, Junglinster/LU



In order to evaluate various SNP's in different genes and chromosomal locations in Caucasian patients as markers of the predisposition to the colorectal cancer (CRC) disease, we analyzed the frequency of different tumour-associated single-nucleotide polymorphisms in several genes including p53 and SMAD7 of Caucasian CRC patients as compared to a healthy Caucasian control population.


Tumour samples were obtained from 188 CRC patients and from leukocytes of 98 healthy control individuals. After gDNA extraction, selected amplicons were amplified by PCR, followed by melting curve analysis. The statistical evaluation was carried out using the Chi-squared test.


Comparing the patients to the controls, a significant difference in the genotype distribution of the G429C SNP in the p53 gene was observed (P = 0.046). Similarly, a significant difference was found for rs4939827 C > T in the SMAD7 gene (P = 0.037), although no significant differences were found for rs4464148 T > C (P = 0.585) or rs12953717 C > T (P = 0.197) also in SMAD7. Differences in genotype distribution for CHR9 C > A rs719725 and CHR8 G > A rs7014346 were almost significant (P = 0.050 and P = 0.054 respectively). Significant results previously reported for two other genes were confirmed:- PAI, 5G vs. 4G, rs1799899 (P = 0.047) and TGFBR1 A > G rs334348, G > A rs334349 and A > C rs1591 (P < 0.0001). No significant differences were found for SNP's in 9 other genes.


The results for p53, SMAD7, PAI, CHR8 and CHR9 are suggestive rather than conclusive and invite confirmation through further study. Concerning the association between the TGFBR1 SNP's and colorectal cancer, the results are significant (p < 0.0001). For example, with the TGFBR1 SNP rs334348, the frequency of the GG genotype was as much as 43% for the CRC patients but 11% for the controls, while the frequency of the AA genotype was only 18% for the patients and 43% for the controls.


All authors have declared no conflicts of interest.