Supplementary Material for: C5orf66 rs4976270/rs639933 Are Associated with Colorectal Cancer Risk in Southern Chinese Han Population: A Case-Control Study

Background: Colorectal cancer (CRC) is one of the common malignant tumors, with high mortality and poor prognosis. Our study aimed to determine the association between the long noncoding RNA (LncRNA) C5orf66 polymorphism and CRC risk in southern Chinese Han population. Method: Using the experimental design of “case-control” study (512 cases and 513 controls), we selected 4 candidate single-nucleotide polymorphisms (SNPs) of C5orf66. All candidate SNPs were genotyped by Agena MassARRAY. Logistic regression was used to analyze the association between SNPs and CRC risk. Then, we used false-positive report probability analysis to detect whether the significant result is just a chance or noteworthy observation. Multi-factor dimensionality reduction was used to analyze the interaction of “SNP-SNP” in CRC risk. Results: Our results showed that C5orf66 SNPs rs4976270 (odds ratio [OR] = 1.69, p = 0.021) and rs639933 (OR = 1.67, p = 0.024) were, respectively, associated with increasing CRC risk in the southern Chinese Han population. Stratified analysis showed that rs4976270 and rs639933 were significantly associated with an increased risk of CRC in subgroups (>60 years, body mass index ≤24 and drinking) under multiple genetic models. In addition, rs254563 and rs647161 also had potential association with CRC risk in subgroups (BMI ≤24 and drinking). Finally, haplotype analysis results showed that haplotype “TA” was significantly associated with increased CRC risk (OR = 1.21, confidence interval = 1.47–2.02, p = 0.043). Conclusion: Our study provides a new idea for the risk assessment of CRC. LncRNA C5orf66 SNPs have a certain association with CRC risk in the southern Chinese Han population.背景：结直肠癌（Colorectal cancer, CRC）是常见恶性肿瘤之一，具有高死亡率与不良预后。本研究旨在探究长链非编码RNA（long noncoding RNA, LncRNA）C5orf66基因多态性与中国南方汉族人群结直肠癌发病风险的关联。方法：本研究采用病例-对照研究（case-control study）实验设计，共纳入512例病例与513例对照，筛选出C5orf66基因的4个候选单核苷酸多态性（single-nucleotide polymorphisms, SNPs）。所有候选SNPs均通过Agena MassARRAY平台完成基因分型。采用logistic回归分析SNPs与结直肠癌发病风险的关联；通过假阳性报告概率（false-positive report probability, FPRP）分析验证显著结果是否为偶然现象或具有统计学意义的发现；采用多因子降维法（multi-factor dimensionality reduction, MDR）分析SNPs间的交互作用对结直肠癌发病风险的影响。结果：本研究结果显示，C5orf66基因的rs4976270（比值比[odds ratio, OR]=1.69，p=0.021）与rs639933（OR=1.67，p=0.024）分别与中国南方汉族人群结直肠癌发病风险升高显著相关。分层分析表明，在多种遗传模型下，rs4976270与rs639933在亚组（年龄>60岁、体质量指数≤24及饮酒人群）中与结直肠癌发病风险升高显著相关。此外，rs254563与rs647161在亚组（体质量指数≤24及饮酒人群）中也显示出与结直肠癌发病风险的潜在关联。最后，单倍型分析结果显示，单倍型“TA”与结直肠癌发病风险升高显著相关（OR=1.21，置信区间=1.47~2.02，p=0.043）。结论：本研究为结直肠癌的风险评估提供了新的思路。LncRNA C5orf66基因多态性与中国南方汉族人群的结直肠癌发病风险存在一定关联。