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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.
摘要：
前列腺癌（PCa）是全球范围内的主要公共卫生问题。最近的研究表明，ghrelin及其受体可能与PCa等多种癌症的易感性有关。导致它们被用作癌症临床进展和预后的重要预测方法。然而,在不同的研究中证明了单核苷酸多态性(SNPs)与ghrelin(GHRL)及其受体(GHSR)基因的相互矛盾的结果.因此，本病例对照研究旨在研究GHRL和GHSR多态性与散发性PCa易感性的相关性.本研究纳入了120名PCa患者和95名健康受试者的队列。使用TaqMan对六个SNP进行基因分型:GHRL中的三个标签SNP(rs696217、rs4684677、rs3491141)和GHSR中的三个标签SNP(rs2922126、rs572169、rs2948694)。等位基因和基因型分布，以及单倍型频率和连锁不平衡(LD)，已建立。使用多因素降维（MDR）分析来研究六个SNP之间的基因-基因相互作用。我们的结果表明目标多态性与PCa没有显着关联（p>0.05）。然而，SNP通常只是帮助鉴定或界定可能带有功能变体而不是导致疾病的变体的特定基因组区域的标记。此外，我们发现一个GHSRrs2922126，即TT基因型，PCa患者明显高于对照组(p=0.040)。这些数据表明该基因型可能是PCa易感性基因型。MDR分析表明，rs2922126和rs572169组合是最好的模型，预测PCa易感性的准确率为81.08%(p=0.0001)。结果还显示了98.1%(p<0.0001)的精确度和1.00的PR-AUC。我们的发现为GHRL和GHSR多态性的影响提供了新的见解，并为PCa易感性中的基因-基因相互作用提供了重要证据。它们可以指导临床决策，以防止过度治疗并提高患者的生活质量。
