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

Abstract

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.

Genetic Risk Score for Prostate Cancer in the Romanian Population

“…However, less is known about whether these associations can be consistently replicated in Eastern European populations (JINGA & al. [15]; ARNOLD & al. [16]).…”

Prostate cancer: an occupational hazard in Romania?

“…The ROMCAN project is a hospital based casecontrol study, conducted in "Carol Davila" University clinics in Bucharest, and aimed to investigate genetic and non-genetic determinants of five major cancer types (colorectal, prostate, breast and lung). Details are described elsewhere [18][19][20].…”

“…Assignment of occupational CAEN codes and grouping study subjects for analysis, based on similarities in exposure, was conducted by experienced occupational health specialists blinded to the subjects' case/control status. By assigning subjects the mean exposure of their group the misclassification bias is attenuated [19] but the method might have entailed errors due to the lack of details on tasks and hazards. The coding of activities up to the 2-digits level of the CAEN classification is also likely to be problematic in terms of validity and reliability of qualitative exposure assessment.…”

Genetic Association Studies on Prostate Cancer

“…Afterward, other studies have provided additional evidence to support the association between 10q11 and PCa susceptibility, including both GWASs and validation studies [49][50][51][52][53][54][55]. One of these PCa risk-associated genetic variants was located in the close proximity of the transcription start site of the gene Microseminoprotein B (MSMB ) which encodes a tumor-suppressor, and was, therefore, even considered as potentially functional.…”