SNPs-Panel Polymorphism Variations in GHRL and GHSR Genes Are Not Associated with Prostate Cancer

Nesrine Merabet; Nicolas Ramoz; Amel Boulmaiz; Asma Bourefis; Maroua Benabdelkrim; Omar Djeffal; Emmanuel Moyse; Virginie Tolle; Hajira Berredjem

doi:10.3390/biomedicines11123276

SNPs-Panel Polymorphism Variations in GHRL and GHSR Genes Are Not Associated with Prostate Cancer

Biomedicines. 2023 Dec 11;11(12):3276. doi: 10.3390/biomedicines11123276.

Authors

Nesrine Merabet^{1

2}, Nicolas Ramoz³, Amel Boulmaiz¹, Asma Bourefis¹, Maroua Benabdelkrim¹, Omar Djeffal⁴, Emmanuel Moyse², Virginie Tolle³, Hajira Berredjem¹

Affiliations

¹ Laboratory of Applied Biochemistry and Microbiology, Department of Biochemistry, Faculty of Sciences, Badji Mokhtar University, Annaba 23000, Algeria.
² Unit 85 PRC (Physiology of Reproduction and Behavior), Centre INRAe of Tours, University of Tours, 37380 Nouzilly, France.
³ University Paris Cité, INSERM U1266, Institute of Psychiatry and Neuroscience of Paris (IPNP), 75014 Paris, France.
⁴ Private Medical Uro-Chirurgical Cabinet, Cité SafSaf, BatR02 n°S01, Annaba 23000, Algeria.

Abstract

Prostate cancer (PCa) is a major public health problem worldwide. Recent studies have suggested that ghrelin and its receptor could be involved in the susceptibility to several cancers such as PCa, leading to their use as an important predictive way for the clinical progression and prognosis of cancer. However, conflicting results of single nucleotide polymorphisms (SNPs) with ghrelin (GHRL) and its receptor (GHSR) genes were demonstrated in different studies. Thus, the present case-control study was undertaken to investigate the association of GHRL and GHSR polymorphisms with the susceptibility to sporadic PCa. A cohort of 120 PCa patients and 95 healthy subjects were enrolled in this study. Genotyping of six SNPs was performed: three tag SNPs in GHRL (rs696217, rs4684677, rs3491141) and three tag SNPs in the GHSR (rs2922126, rs572169, rs2948694) using TaqMan. The allele and genotype distribution, as well as haplotypes frequencies and linked disequilibrium (LD), were established. Multifactor dimensionality reduction (MDR) analysis was used to study gene-gene interactions between the six SNPs. Our results showed no significant association of the target polymorphisms with PCa (p > 0.05). Nevertheless, SNPs are often just markers that help identify or delimit specific genomic regions that may harbour functional variants rather than the variants causing the disease. Furthermore, we found that one GHSR rs2922126, namely the TT genotype, was significantly more frequent in PCa patients than in controls (p = 0.040). These data suggest that this genotype could be a PCa susceptibility genotype. MDR analyses revealed that the rs2922126 and rs572169 combination was the best model, with 81.08% accuracy (p = 0.0001) for predicting susceptibility to PCa. The results also showed a precision of 98.1% (p < 0.0001) and a PR-AUC of 1.00. Our findings provide new insights into the influence of GHRL and GHSR polymorphisms and significant evidence for gene-gene interactions in PCa susceptibility, and they may guide clinical decision-making to prevent overtreatment and enhance patients' quality of life.

Keywords: GHRL; GHSR; MDR; SNPs; genetic polymorphisms; prostate cancer.

Grants and funding

Nesrine Merabet was supported by a doctoral grant (Profas B+) from the University of Tours, France, and University of Badji Mokhtar, Annaba, Algeria. This work was financially co-supported by the Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, 75014, Paris, France, and by the Algerian Ministry of High Education and Scientific Research, under the National Research Project PRFU: D01N01UN230120200005.