Chen Fa, He Baochang, Yan Lingjun, Qiu Yu, Lin Lisong, Cai Lin
Doctoral Candidate, Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.
Associate Professor, Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.
J Oral Maxillofac Surg. 2017 Jan;75(1):214-220. doi: 10.1016/j.joms.2016.07.005. Epub 2016 Jul 25.
The fatty acid desaturase 1 (FADS1) gene variant is a novel susceptibility marker for laryngeal squamous cell carcinoma identified by a recent genome-wide association study, but it is still unclear whether this genetic variant continues to influence oral cancer recurrence or death. The purpose of this study was to evaluate the role of FADS1 rs174549 polymorphism and its interaction with postoperative chemoradiotherapy in the prognosis of oral cancer.
A prospective cohort study involving 304 oral cancer patients with surgical resection was conducted in Fujian, China. Demographic and clinical data (adjuvant therapy types, histologic types, clinical stage, etc.) were extracted from medical records, and follow-up data were obtained by telephone interviews. We collected 5 to 8 mL of venous blood from all patients for DNA extraction, and rs174549 genotypes were determined by TaqMan assays (Life Technologies, Carlsbad, CA). A Cox proportional hazards model and Kaplan-Meier curve were used to assess the association between FADS1 rs174549 polymorphism and progression-free survival (PFS), as well as overall survival, in oral cancer.
Carrying the AA genotype was significantly associated with a decreased risk of PFS: The hazard ratio was 0.52 (95% confidence interval, 0.29 to 0.93) for the codominant model and 0.54 (95% confidence interval, 0.31 to 0.94) for the recessive model. Moreover, better PFS was particularly obvious in patients who had received chemoradiotherapy. A positive multiplicative interaction between FADS1 rs174549 polymorphism and chemoradiotherapy was observed for PFS (P = .036). No significant association was found between FADS1 rs174549 polymorphism and overall survival.
Our study suggests, for the first time, that FADS1 rs174549 polymorphism is a potentially independent and favorable factor in predicting oral cancer PFS especially for patients who undergo chemoradiotherapy, and it may serve as a potential target for individualized treatment in the future.
脂肪酸去饱和酶1(FADS1)基因变异是最近一项全基因组关联研究确定的喉鳞状细胞癌新的易感标志物,但该基因变异是否继续影响口腔癌复发或死亡仍不清楚。本研究的目的是评估FADS1 rs174549多态性及其与术后放化疗的相互作用在口腔癌预后中的作用。
在中国福建对304例接受手术切除的口腔癌患者进行了一项前瞻性队列研究。从病历中提取人口统计学和临床数据(辅助治疗类型、组织学类型、临床分期等),并通过电话访谈获得随访数据。我们从所有患者中采集5至8毫升静脉血用于DNA提取,并通过TaqMan分析(Life Technologies,卡尔斯巴德,加利福尼亚州)确定rs174549基因型。采用Cox比例风险模型和Kaplan-Meier曲线评估FADS1 rs174549多态性与口腔癌无进展生存期(PFS)以及总生存期之间的关联。
携带AA基因型与PFS风险降低显著相关:共显性模型的风险比为0.52(95%置信区间,0.29至0.93),隐性模型的风险比为0.54(95%置信区间,0.31至0.94)。此外,接受放化疗的患者PFS更好尤为明显。观察到FADS1 rs174549多态性与放化疗之间在PFS方面存在正相乘交互作用(P = 0.036)。未发现FADS1 rs174549多态性与总生存期之间存在显著关联。
我们的研究首次表明,FADS1 rs174549多态性是预测口腔癌PFS的一个潜在独立且有利的因素,尤其是对于接受放化疗的患者,并且它可能在未来成为个体化治疗的潜在靶点。