文章：

胆囊癌风险与南美原住民马普切血统：使用血统信息标记的工具变量分析

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers

原文发布日期：9 August 2023

DOI: 10.3390/cancers15164033

类型: Article

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英文摘要：

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%,p= 6.7 × 10−5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate −0.006 kg/m2, 95% CI −0.009 to −0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

摘要翻译： 

观察性研究报告显示，南美洲土著马普切人血统比例与胆囊癌风险之间存在显著关联。智利人的胆囊癌发病率位居全球首位，而马普切人是智利最大的土著族群。本研究旨在评估个体马普切血统比例对胆囊癌风险的无混杂效应，并探究胆石症与体质指数在此关联中的中介作用。我们基于信息性分配指标筛选马普切血统的遗传标记，将其作为工具变量进行双样本孟德尔随机化分析和敏感性补充分析。结果显示马普切血统对胆囊癌风险存在推定因果效应（马普切血统比例每增加1%，逆方差加权风险增加0.8%，95% CI 0.4%至1.2%，p=6.7×10^−5），对胆石症亦存在显著效应（逆方差加权风险增加3.6%，95% CI 3.1%至4.0%），表明胆石症在马普切血统与胆囊癌关联中起中介作用。相反，马普切血统比例对体质指数呈负向影响（逆方差加权估计值-0.006 kg/m^2，95% CI -0.009至-0.003）。本研究结果对胆囊癌预防具有重要启示，并为后续混合映射研究提供关键依据。鉴于观察性研究中发现的个体马普切血统比例与胆囊癌风险关联不存在混杂因素，纳入遗传血统考量的一级与二级预防策略可能具有显著效益。

原文链接：

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers