Annals of Oncology, Vol. 23, Suppl. 4, 2012
Annals of Oncology, Vol. 23, Suppl. 4 (2012), page iv17, abstract number O-0017
M. Pauly1, B. Metzger1, G. Mahon1, M. Dicato1, A. Menzel2 and B. Weber2.
1 Centre Hospitalier de Luxembourg, Recherche sur le cancer et les maladies du sang, Luxembourg, Luxembourg.
2 Laboratoires Réunis, Junglinster, Luxembourg.
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 at the adenocarcinoma stage and from 98 healthy control individuals. After gDNA extraction, selected amplicons were amplified by PCR, followed by melting curve analysis. The statistical evaluation of the difference in genotype frequency at the different SNPs comparing CRC patients with healthy controls was carried out using the Chi-squared test.
When analyzing 188 tumour samples and comparing with 98 healthy 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, on the other hand, the results are already clear. 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.
Annals of Oncology, Vol. 22, Suppl. 5, 2011
Annals of Oncology, Volume 22, Supplement 5, 2011, page 11, number O-0004
O-0004 THE TGFBR1 GENE HAS A HIGHLY SIGNIFICANT MUTATION FREQUENCY AT SEVERAL SINGLE NUCLEOTIDE POLYMORPHISM (SNP) MARKER SITES IN CAUCASIAN PATIENTS WITH ADVANCED COLORECTAL CANCER AS COMPARED TO HEALTHY CONTROLS
Marc Pauly1, Alain Menzel2, Natacha Van der Taelem2, Brigitte Metzger1, Laetitia Chambeau1, Jacques Kayser3, Carlo Faber3, Petr Nazarov4, Laurent Vallar4, Bernard Weber2, Mario Antoine Dicato1
1Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Fondation de Recherche Cancer et Sang, Luxembourg, Luxembourg,
2Laboratoires Réunis de Junglinster, Junglinster, Luxembourg,
3Clinique Ste-Thérèse, Luxembourg, Luxembourg,
4Microarray Center, Centre de Recherche Public de la Santé, Luxembourg, Luxembourg.
In order to evaluate various SNPs in different genes and chromosomal locations in caucasian patients as markers linked to the predisposition of the colorectal cancer (CRC) disease, we analyzed the frequency of different tumour-associated single-nucleotide polymorphisms in the following genes: p53 [G429C], mdm2 [G309T], TGFßR1 (rs334348, A>G; rs334349, G>A; rs1591, A>C), SMAD7 (rs4464148, T>C; rs12953717, C>T; rs4939827, C>T), FLJ (rs3802842, A>C) as well as CHR8 (rs7014346, G>A; 8q24 rs6983267, T>G) and CHR9 (rs719725, C>A) chromosomal locations of 100 caucasian CRC patients as compared to a caucasian healthy population.
Tumour samples were obtained from caucasian CRC patients at the adenocarcinoma stage and from caucasian healthy individuals. After gDNA extraction, selected amplicons were amplified by PCR, followed by melting curve analysis. The statistical evaluation of the mutation frequency at the different SNPs while comparing CRC patients versus healthy individuals was calculated following the Chi-squared test.
When analyzing 100 tumour samples and comparing with a healthy population to estimate the genotype distribution and mutation frequency in CRC cases, the most highly significant mutation frequency occurred at three TGFßR1 SNPs (rs334348, rs334349, rs1591, p=0,00000) and a still significant frequency at the chromosomal CHR8 (rs7014346, p=0,03452) and CHR9 (rs719725, p=0,02867) locations. However, the mutation frequencies at all the other analyzed SNP sites were not significant.
As shown by this study, SNPs rs334348, rs334349, rs1591 in the tumor growth factor beta receptor 1 (TGFßR1) revealed as the most significant markers and thus strong risk factors linked to the predisposition and/or occurrence of CRC in caucasian patients, followed by SNPs rs719725 and rs7014346 at chromosome 9 and 8, respectively.