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Zollner, L.* ; Boekstegers, F.* ; Barahona Ponce, C.* ; Scherer, D.* ; Marcelain, K.* ; Garate-Calderon, V.* ; Waldenberger, M. ; Morales, E.* ; Rojas, A.* ; Muñoz, C.* ; Retamales, J.* ; de Toro, G.* ; Kortmann, A.V.* ; Barajas, O.* ; Rivera, M.T.* ; Cortes, A.* ; Loader, D.* ; Saavedra, J.* ; Gutierrez, L.* ; Ortega, A.* ; Bertran, M.E.* ; Bartolotti, L.* ; Gabler, F.* ; Campos, M.* ; Alvarado, J.* ; Moisán, F.* ; Spencer, L.* ; Nervi, B.* ; Carvajal, D.* ; Losada, H.* ; Almau, M.* ; Fernandez, P.* ; Olloquequi, J.* ; Carter, A.R.* ; Miquel Poblete, J.F.* ; Bustos, B.I.* ; Fuentes Guajardo, M.* ; Gonzalez-Jose, R.* ; Bortolini, M.C.* ; Acuña-Alonzo, V.* ; Gallo, C.* ; Ruiz Linares, A.* ; Rothhammer, F.* ; Lorenzo Bermejo, J.*

Gallbladder cancer risk and indigenous South American Mapuche ancestry : Instrumental variable analysis using ancestry-informative markers.

Cancers 15:17 (2023)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Mendelian Randomization ; Ancestry-informative Markers ; Causal Inference ; Gallbladder Cancer ; Gallstone Disease ; Genetic Admixture ; Indigenous South American Mapuche Ancestry ; Instrumental Variables; Epidemiology; Admixture; Cholelithiasis; History

ISSN (print) / ISBN 2072-6694

Journal Cancers

Quellenangaben Volume: 15, Issue: 16, Article Number: 17

Publisher MDPI

Publishing Place St Alban-anlage 66, Ch-4052 Basel, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)

Grants German Research Foundation (DFG)
Ministry of Science, Research, and the Arts Baden-Wurttemberg