Artículo
Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers
Zollner, Linda; Boekstegers, Felix; Barahona Ponce, Carol; Scherer, Dominique; Marcelain, Katherine; Gárate Calderón, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Muñoz, César; Alvarado, Juan; Moisán, Fabricio; Spencer, Loreto; Nervi, Bruno; Carvajal, Daniel; Losada, Héctor; Almau, Mauricio; Fernández, Plinio; Olloquequi, Jordi; Carter, Alice R.; Miquel Poblete, Juan Francisco; Bustos, Bernabe Ignacio; Fuentes Guajardo, Macarena; Gonzalez-Jose, Rolando
; Bortolini, Maria Cátira; Acuña Alonzo, Victor; Gallo, Carla; Ruiz-Linares, Andres; Rothhammer, Francisco; Lorenzo Bermejo, Justo
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
08/2023
Editorial:
Multidisciplinary Digital Publishing Institute
Revista:
Cancers
e-ISSN:
2072-6694
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
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Articulos(IPCSH)
Articulos de INSTITUTO PATAGONICO DE CIENCIAS SOCIALES Y HUMANAS
Articulos de INSTITUTO PATAGONICO DE CIENCIAS SOCIALES Y HUMANAS
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Zollner, Linda; Boekstegers, Felix; Barahona Ponce, Carol; Scherer, Dominique; Marcelain, Katherine; et al.; Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers; Multidisciplinary Digital Publishing Institute; Cancers; 15; 16; 8-2023; 1-17
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