Supplementary Material for: Effect of Germline MEFV polymorphisms on the prognosis of Japanese children with cancer: A regional analysis

Introduction: MEFV is the gene responsible for familial Mediterranean fever (FMF). It encodes pyrin, which controls inflammation; Besides, previous studies have reported that some germline MEFV variants were associated with tumour susceptibility. Materials and Methods: The loci of 12 germline MEFV variants were genotyped in 153 Japanese children with cancer, and the frequencies of these variants among the patient groups were compared with those in the general Japanese population. Additionally, the relationship between these variants and clinical data, including relapse and death, was investigated. Results: Minor allele frequencies did not differ between patients and the general population, or between sex, age at diagnosis, and diagnosis among patients. P369S/R408Q associated with significantly lower relapse-free survival in all patient analyses and in patients with solid tumours. Additionally, although the results were not significant, E148Q/L110P was likely to associate with worse relapse-free survival in patients with solid tumours. Discussion/Conclusion: Despite several limitations, this study provided the novel insight that the germline MEFV variants are associated with the clinical outcome of paediatric cancer.

引言：MEFV基因是家族性地中海热（familial Mediterranean fever, FMF）的致病基因，其编码的pyrin蛋白（pyrin）可调控炎症反应。此外，既往研究表明，部分生殖系MEFV变异与肿瘤易感性相关。
材料与方法：本研究对153例日本儿童癌症患者的12种生殖系MEFV变异位点进行基因分型，并将患者队列中这些变异的频率与日本普通人群的对应频率进行对比。此外，本研究还分析了这些变异与复发、死亡等临床数据之间的关联。
结果：患者组与普通人群之间，以及患者内部按性别、诊断年龄、诊断类型分组之间的次要等位基因频率（minor allele frequency, MAF）均无显著差异。P369S/R408Q变异与所有患者队列及实体瘤患者的无复发生存期显著缩短相关。此外，尽管结果未达到统计学显著性，但E148Q/L110P变异可能与实体瘤患者更差的无复发生存期相关。
讨论与结论：尽管本研究存在若干局限性，但本研究提供了生殖系MEFV变异与儿童癌症临床结局相关的新见解。