复合维生素和矿物质补充对上消化道肿瘤死亡风险的影响:林县食管鳞状上皮重度增生人群营养干预试验35年随访结果

Multivitamins and Minerals Supplementation and the Long-term Risk of Upper Gastrointestinal Cancer Mortalityin Esophageal Squamous Severe Dysplasia Population:a 35-year Follow-up Study in Linxian Dysplasia Nutrition Intervention Trial

[目的]分析中国林县营养干预试验队列食管鳞状上皮重度增生人群(以下简称重增人群)35年随访数据资料,探究复合维生素与矿物质补充与上消化道肿瘤长期死亡风险之间的关系。[方法]林县重增人群营养干预试验是一项随机、双盲、安慰剂对照试验。研究选取3318名40~69岁重增人群为受试者,进行为期6年的营养干预并随访至2020年4月30日。以食管癌、贲门癌、非贲门胃癌死亡为研究终点,采用COX风险比例回归模型估计研究对象发生上消化道肿瘤死亡事件的风险比和95%可信区间(95%CI)。[结果]在35年的随访过程中,共发生上消化道肿瘤死亡952例。其中,食管癌死亡572例,贲门癌死亡299例,非贲门胃癌死亡81例。与安慰剂组相比,营养干预组的上消化道肿瘤死亡风险并未显著下降(HR=0.94,95%CI:0.83~1.07)。在不同性别及年龄的受试者中均未观察到复合维生素和矿物质对上消化道肿瘤死亡风险的保护效应(HR_(male)=0.87,95%CI:0.73~1.04;HR_(female)=0.96,95%CI:0.82~1.18;HR_(age)<55=0.88,95%CI:0.74~1.04;HR_(age)≥55=0.99,95%CI:0.82~1.19)。在年龄<55岁的男性受试者中,营养干预使上消化道肿瘤死亡风险降低24%,差异具有统计学意义(HR=0.76,95%CI:0.58~0.98)。未观察到营养干预对不同年龄段女性上消化道肿瘤死亡风险的保护作用。[结论]服用复合维生素和矿物质并不能降低重增人群的上消化道肿瘤死亡风险。需要进行进一步研究以验证营养干预的作用。

[Purpose] To investigate the association between multivitamins and minerals supplementation and the long-term risk of upper gastrointestinal(UGI) cancer mortality in esophageal squamous severe dysplasia population by analyzing the 35-year follow-up data of the Linxian dysplasia nutrition intervention trial(NIT) cohort.[Methods] The NIT was a randomized,double-blind,placebo-controlled trial. A total of 3318 subjects aged 40 to 69 years with esophageal squamous server dysplasia received nutrition intervention for 6 years and were followed up until April 30, 2020.The primary endpoints were esophageal squamous cell carcinoma(ESCC),gastric cardia carcinoma(GCC),and non-cardia gastric carcinoma(NCGC) death. Cox proportional hazard model was used to estimate hazard ratio(HR) and 95% confidence interval(95%CI). [Results] During the 35-year follow-up,a total of 952 UGI cancer deaths occurred,including 572 ESCC-related,299-GCC related,and 81 NCGC-related deaths. Compare to placebo group,the long-term risk of UGI cancer mortality in nutrition intervention group did not decrease significantly(HR =0.94,95% CI:0.83 ~1.07).Multivitamins and minerals supplementation did not affect participants’ UGI cancer mortality in different gender or age groups(HR_(male)=0.87,95%CI:0.73~1.04;HRf_(emale)=0.96,95%CI:0.82~1.18;HR_(age)<55=0.88,95%CI:0.74~1.04;HR_(age)≥55=0.99,95%CI:0.82~1.19). Nutrition intervention reduced UGI cancer mortality by 24% among men under 55,and the difference was statistically significant(HR =0.76,95% CI:0.58 ~0.98). No effect was observed for deaths from UGI cancer in women of different age groups. [Conclusion] Taking multivitamins and minerals could not reduce the risk of death from UGI cancer among the esophageal squamous severe dysplasia population. Further studies need to be carried out to validate the effect of nutrition intervention.