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. 2023 Oct 13;21(1):391.
doi: 10.1186/s12916-023-03104-1.

Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer

Katharina Nimptsch  1 , Krasimira Aleksandrova  2   3 , Thu Thi Pham  4   5 , Nikos Papadimitriou  6 , Jürgen Janke  4   7 , Sofia Christakoudi  8   9 , Alicia Heath  8 , Anja Olsen  10   11 , Anne Tjønneland  10   12 , Matthias B Schulze  13   14 , Verena Katzke  15 , Rudolf Kaaks  15 , Bethany van Guelpen  16   17 , Justin Harbs  16 , Domenico Palli  18 , Alessandra Macciotta  19 , Fabrizio Pasanisi  20 , Sandra Milena Colorado Yohar  21   22   23 , Marcela Guevara  22   24   25 , Pilar Amiano  22   26   27 , Sara Grioni  28 , Paula Gabriela Jakszyn  29   30 , Jane C Figueiredo  31 , N Jewel Samadder  32 , Christopher I Li  33 , Victor Moreno  22   34   35 , John D Potter  33   36 , Robert E Schoen  37 , Caroline Y Um  38 , Elisabete Weiderpass  39 , Mazda Jenab  6 , Marc J Gunter  6 , Tobias Pischon  4   5   7
Affiliations

Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer

Katharina Nimptsch et al. BMC Med. .

Abstract

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.

Keywords: Colorectal cancer; FABP-4; Mendelian randomization.

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Conflict of interest statement

Marc J. Gunter is a member of the editorial board for BMC Medicine. The other authors declare no potential conflicts of interest.

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