TY - JOUR
T1 - Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
AU - Nimptsch, Katharina
AU - Aleksandrova, Krasimira
AU - Pham, Thu Thi
AU - Papadimitriou, Nikos
AU - Janke, Jürgen
AU - Christakoudi, Sofia
AU - Heath, Alicia
AU - Olsen, Anja
AU - Tjønneland, Anne
AU - Schulze, Matthias B.
AU - Katzke, Verena
AU - Kaaks, Rudolf
AU - van Guelpen, Bethany
AU - Harbs, Justin
AU - Palli, Domenico
AU - Macciotta, Alessandra
AU - Pasanisi, Fabrizio
AU - Yohar, Sandra Milena Colorado
AU - Guevara, Marcela
AU - Amiano, Pilar
AU - Grioni, Sara
AU - Jakszyn, Paula Gabriela
AU - Figueiredo, Jane C.
AU - Samadder, N. Jewel
AU - Li, Christopher I.
AU - Moreno, Victor
AU - Potter, John D.
AU - Schoen, Robert E.
AU - Um, Caroline Y.
AU - Weiderpass, Elisabete
AU - Jenab, Mazda
AU - Gunter, Marc J.
AU - Pischon, Tobias
N1 - Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/12
Y1 - 2023/12
N2 - Background: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach. Methods: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Results: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37). Conclusions: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.
AB - Background: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach. Methods: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Results: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37). Conclusions: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.
KW - Colorectal cancer
KW - FABP-4
KW - Mendelian randomization
UR - http://www.scopus.com/inward/record.url?scp=85174314339&partnerID=8YFLogxK
U2 - 10.1186/s12916-023-03104-1
DO - 10.1186/s12916-023-03104-1
M3 - Article
C2 - 37833736
AN - SCOPUS:85174314339
SN - 1741-7015
VL - 21
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 391
ER -
