Kategorie: Onkologická diagnostika
Číslo abstraktu: 0976
Background: KRAS is one of the most frequently mutated oncogenes in human cancer, with almost a quarter of different tumor types showing altered functions of KRAS. The let-7 family of microRNAs were found to regulate KRAS activity by binding to the 3'UTR of human KRAS gene. A germline SNP (rs61764370) is located in a let-7 complementary site (LCS6) in the 3'UTR of KRAS oncogene. The LCS6 SNP consists of a T-to-G base change and it was found to alter the binding capability of the mature let-7 miRNA to the KRAS mRNA. In several studies G-allele of rs61764370 was found to be associated with higher risk of breast cancer, colorectal cancer, melanoma, oral cancer and ovarian cancer. It is potential biomarker of poor response to targeted therapies in colon cancer too. Controversially, other authors did not find significant association with cancer risk. Thus, the relevance of rs61764370 in cancer predisposition is still debated and deserves further investigations.
Material and Methods: DNA of tumours tissues was isolated from fixed, fresh-frozen, cytology specimens and formaline fixed paraffin embedded tissue from 262 mCRC, 158 breast and 117 NSCLC patients. DNA from 387 healthy controls was isolated from peripheral blood. Analysis of SNP rs61764370 (KRAS-LCS6) was performed by PCR and RFLP method.
Results: The KRAS-LCS6 G-allele (T/G genotype) was detected in 9.9% (26/262) of mCRC cases; 15.2% (24/158) of breast cancer cases and 14.5% (17/117) of NSCLC patients. T/G genotype of the SNP (rs61764370) was identified in 15.8% (61/387) of healthy controls. In our study we did not find G-allele carriers in homozygous state (G/G genotype) among the cancer patients and healthy controls.
Conclusions: The frequency of the LCS6 G-allele varies across geographic populations, with European populations exhibiting the variant allele most frequently 5–10%. In our study, in healthy Czech population (controls), frequency the LCS6 G- allele was 15.8%. Prevalence of the KRAS-LCS6 G-allele was not significantly different among stadied tumours (NSCLC, breast cancer) and the healthy controls. The acquisition of new data from different populations could have a paramount importance to establish the real contribution of each polymorphism to the cancer risk. The study of polymorphisms, affecting miRNA-dependent pathways and involved in cancer susceptibility is rapidly growing and is becoming increasingly important on the fast growing field of the personalized medicine.
No conflict of interest.
Datum přednesení příspěvku: 27. 9. 2013