Association between RNASEL, MSR1, and ELAC2 single nucleotide polymorphisms and gene expression in prostate cancer risk.
There is contradictory evidence of the effects that environmental factors-dietary habits (ingestion rates of red meat, soy products, fish, etc.) and work environment (exposure to metals, pesticides, several toxic products, etc.)-and KLK3, AR, RNASEL, MSR1, and ELAC2 expression patterns have on prostate cancer (PCa). In our study, we investigated the potential association between KLK3, AR, RNASEL, MSR1, and ELAC2 polymorphisms, expression patterns, exposure to environmental factors, and PCa in a Spanish cohort. Blood and fresh tissue samples were collected from 322 subjects with prostate-specific antigen (PSA)>4ng/ml to determine their genotypes (RNASEL, MSR1, and ELAC2) and assess messenger ribonucleic acid expression levels (by quantitative amplification testing).



Among clinical parameters, a 63.6% of patients with CC variants in rs11545302 (ELAC2) had PSA>20ng/ml (P = 0.008), and rs486907 (RNASEL), with 52.8% of patients with CT variants with Gleason score>7. Regarding TNM stage, patients with GG variants, rs4792311 (ELAC2) generally had stage 1 tumors. Genetic expression analysis revealed RNASEL (P = 0.007) was underexpressed in PCa tissue, whereas KLK3 (P = 0.041) was overexpressed. As to environmental factors, the intake of dried fruits (P = 0.036) and practice of sports (P = 0.024) revealed an effect in PCa. Moreover, environmental factors were observed to affect gene expression patterns. Thus, RNASEL (P = 0.018) and ELAC2 (P = 0.023) were found to be underexpressed in patients who ate processed foods frequently; MSR1 (P = 0.024) and AR (P = 0.004) were underexpressed in patients who did not practice sports; and KLK3 (P = 0.039; P = 0.046) underexpressed in patients exposed to dust and toxic products.



This is the first study to analyze the correlation between RNASEL, MSR1, and ELAC2 genotypes and messenger ribonucleic acid expression in PCa. RNASEL and KLK3 show different expression patterns in normal vs. tumor tissue, which supports their reported relevance in human cancer. The results obtained confirm that RNASEL plays a crucial role in PCa. Environmental factors such as exercise, exposure to toxic agents, and intake of processed foods are associated with PCa.
Liquid biopsy and metastasis research group and Genomic Unit, GENyO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain. Electronic address: mjesusac@ugr.es.
Maria Jesus
MJ
Alvarez-Cubero
Service of Urology, University Hospital Virgen de las Nieves, Granada, Spain.
Manrique
M
Pascual-Geler
Liquid biopsy and metastasis research group and Genomic Unit, GENyO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain.
Luis Javier
LJ
Martinez-Gonzalez
Fundación para la Investigación Biosanitaria de Andalucía Oriental-Alejandro Otero (FIBAO), Hospital Virgen de las Nieves, Granada, Spain.
Manuela
M
Expósito Ruiz
Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain.
Maria
M
Saiz
Service of Urology, University Hospital Virgen de las Nieves, Granada, Spain.
Jose Manuel
JM
Cozar
Liquid biopsy and metastasis research group and Genomic Unit, GENyO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain; Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain.
Jose Antonio
JA
Lorente
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D004032:Diet; D004391:Dust; D004722:Endoribonucleases / Q000235:genetics*; D004781:Environmental Exposure; D005638:Fruit; D015870:Gene Expression; D059647:Gene-Environment Interaction; D005838:Genotype; D018095:Germ-Line Mutation; D015386:Hazardous Substances; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D012307:Risk Factors; D051117:Scavenger Receptors, Class A / Q000235:genetics*; D013030:Spain; D013177:Sports / Q000502:physiology; D011795:Surveys and Questionnaires
D014408:Biomarkers, Tumor; D004391:Dust; C421605:ELAC2 protein, human; D015386:Hazardous Substances; C495139:MSR1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
Biomarker; Expression; Prostate cancer; SNP; mRNA