Journal Article

DKFZ-2024-01916

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Characterization of additive gene-environment interactions for colorectal cancer risk.

Thomas, C. E. ; Lin, Y. ; Kim, M. ; Kawaguchi, E. S. ; Qu, C. ; Um, C. Y. ; Lynch, B. M. ; Van Guelpen, B. ; Tsilidis, K. ; Carreras-Torres, R. ; van Duijnhoven, F. J. ; Sakoda, L. C. ; Campbell, P. T. ; Tian, Y. ; Chang-Claude, J.DKFZ* ; Bézieau, S. ; Budiarto, A. ; Palmer, J. R. ; Newcomb, P. A. ; Casey, G. ; Le Marchand, L. ; Giannakis, M. ; Li, C. I. ; Gsur, A. ; Newton, C. ; Obón-Santacana, M. ; Moreno, V. ; Vodicka, P. ; Brenner, H.DKFZ* ; Hoffmeister, M.DKFZ* ; Pellatt, A. J. ; Schoen, R. E. ; Dimou, N. ; Murphy, N. ; Gunter, M. J. ; Castellví-Bel, S. ; Figueiredo, J. C. ; Chan, A. T. ; Song, M. ; Li, L. ; Bishop, D. T. ; Gruber, S. B. ; Baurley, J. W. ; Bien, S. A. ; Conti, D. V. ; Huyghe, J. R. ; Kundaje, A. ; Su, Y.-R. ; Wang, J. ; Keku, T. O. ; Woods, M. O. ; Berndt, S. I. ; Chanock, S. J. ; Tangen, C. M. ; Wolk, A. ; Burnett-Hartman, A. ; Wu, A. H. ; White, E. ; Devall, M. A. ; Díez-Obrero, V. ; Drew, D. A. ; Giovannucci, E. ; Hidaka, A. ; Kim, A. E. ; Lewinger, J. P. ; Morrison, J. ; Ose, J. ; Papadimitriou, N. ; Pardamean, B. ; Peoples, A. R. ; Ruiz-Narvaez, E. A. ; Shcherbina, A. ; Stern, M. C. ; Chen, X. ; Thomas, D. C. ; Platz, E. A. ; Gauderman, W. J. ; Peters, U. ; Hsu, L.

2025
Wolters Kluwer Health, Lippincott Williams & Wilkins Baltimore, Md.

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Please use a persistent id in citations: doi:10.1097/EDE.0000000000001795

Abstract: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk.There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility.Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

Note: 2025 Jan 1;36(1):126-138

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. Präventive Onkologie (C120)
4. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2024

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Current Contents - Social and Behavioral Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Social Sciences Citation Index ; Web of Science Core Collection

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