Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's A1B 3V6, Canada.
Cancer Biol Med. 2023 Jun 6;20(6):438-51. doi: 10.20892/j.issn.2095-3941.2022.0635.
Leptin (LEP) is an obesity-associated adipokine associated with tumor cell growth. We examined the relevance of genetic variants of and leptin receptor () to colorectal cancer (CRC) survival by using data from the Newfoundland Familial Colorectal Cancer Study.
A total of 532 patients newly diagnosed with CRC between 1997 and 2003 were followed up until April 2010. Data on their demographics and lifestyles were collected questionnaires. Genotyping of blood samples was performed with the Illumina Human Omni-Quad Bead chip. Multivariable Cox models were used to assess the relationships of 35 tag single-nucleotide polymorphisms (SNPs) in and with overall survival (OS), disease-free survival (DFS), and CRC-specific survival.
At the gene level, was associated with DFS ( = 0.017), and was associated with both DFS ( = 0.021) and CRC-specific survival ( = 0.013) in patients with CRC. In single-SNP analysis, rs11763517, rs9436301, and rs7602 were associated with DFS after adjustment for multiple testing. The haplotypes G-C-T (rs7534511-rs9436301-rs1887285) and A-A-G (rs7602-rs970467-rs9436748) were associated with prolonged OS among patients with CRC overall (G-C-T: HR, 0.63; 95% CI, 0.43-0.93; A-A-G: HR, 0.59; 95% CI, 0.38-0.91) and those diagnosed with colon cancer (G-C-T: HR, 0.54; 95% CI, 0.34-0.86; A-A-G: HR, 0.49; 95% CI, 0.29-0.83). Similar results were observed for DFS. Moreover, significant interactions were found among rs7602 (A G), rs1171278 (T . C), red meat intake, and BMI status: the associations between these variants and prolonged DFS were limited to patients with below-median red meat consumption and body mass index (BMI) < 25 kg/m.
Polymorphic variations in the and genes were associated with survival of patients after CRC diagnosis. The /-CRC survival association was modified by participants' red meat intake and BMI.
瘦素（LEP）是一种与肿瘤细胞生长相关的肥胖相关脂肪因子。我们通过使用纽芬兰家族结直肠癌研究的数据，检查了和瘦素受体（）的遗传变异与结直肠癌（CRC）生存的相关性。
1997 年至 2003 年间新诊断为 CRC 的 532 例患者，随访至 2010 年 4 月。通过问卷收集他们的人口统计学和生活方式数据。使用 Illumina Human Omni-Quad Bead 芯片对血液样本进行基因分型。多变量 Cox 模型用于评估 35 个标记单核苷酸多态性（SNP）在和中的关系与总生存（OS）、无病生存（DFS）和 CRC 特异性生存。
在基因水平上，与 DFS 相关（=0.017），与 DFS（=0.021）和 CRC 特异性生存（=0.013）相关。在单 SNP 分析中，rs11763517、rs9436301 和 rs7602 在调整多重检验后与 DFS 相关。在所有 CRC 患者中，与 OS 延长相关的是（rs7534511-rs9436301-rs1887285）和（rs7602-rs970467-rs9436748）的 haplotypes G-C-T 和 A-A-G（G-C-T：HR，0.63；95%CI，0.43-0.93；A-A-G：HR，0.59；95%CI，0.38-0.91）和那些被诊断为结肠癌的患者（G-C-T：HR，0.54；95%CI，0.34-0.86；A-A-G：HR，0.49；95%CI，0.29-0.83）。DFS 也观察到类似的结果。此外，还发现了与之间的显著相互作用rs7602（A G）、rs1171278（T. C）、红肉摄入量和 BMI 状态：这些变异与延长 DFS 的关联仅限于中位数以下的红肉消耗和 BMI<25kg/m 的患者。
和基因多态性与 CRC 患者诊断后的生存有关。/CRC 生存的相关性受参与者的红肉摄入量和 BMI 状态的影响。
