At the end of the project, we will have created a unique database and biobank for cancer research in the Romanian population, including an assembly of a nested case control study of Roma ethnics. We will have profiled of the common genetic variation underlying LuCa, PrCa, CRC and BrCa in Romania and potentially uncovered and validated additional risk variants. Importantly, we will have taken the first steps towards defining the spectrum of high-risk mutations BrCa and CRC. Collectively, these studies will lead to a better understanding of genetic susceptibility to cancer in Romania and will have immediate use for screening in high-risk families. The project results will catalogue the population frequencies of common genetic variation in Romania which is of use for other geneticists in the country. Last, but not least, the project will raise the profile of cancer research in Romania at the international level and increase the possibility of attracting additional funding. In the long-term, research on the epidemiological and genetic causes of cancer will be useful for policy makers and may impact strategies to lessen the burden of cancer and improve public health.

Review of genetics literature in Romania

 

A comprehensive analysis of genome-wide association studies to identify prostate cancer susceptibility loci for the Romanian population

(Radavoi GD, Pricop C, Jinga V, Mates D, Radoi VE, Jinga M, Ursu RI, Bratu OG, Mischianu DL, Iordache P)

The aim of this study is to examine a large dataset of single nucleotide polymorphism known to be associated with prostate cancer from previous genome-wide association studies and create a dataset of single nucleotide polymorphisms that can be used in replication studies for the Romanian population. This study will define a list of markers showing a significant association with this phenotype. We propose the results of this study as a starting point for any Romanian genome-wide association studies researching the genetic susceptibility for prostate cancer.

Replication study of 34 common SNPs associated with prostate cancer in the Romanian population

(Jinga V, Csiki IE, Manolescu A, Iordache P, Mates IN, Radavoi D, Rascu S, Badescu D, Badea P, Mates D)

Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP’s with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.