Abstract
Methods: Information was leveraged from GWAS regarding PUFA-associated single nucleotide polymorphisms (SNPs) to create weighted genetic scores (wGSs) representing genetically-predicted circulating blood PUFAs for 11,016 non-Hispanic white CRC cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per standard deviation increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on CRC risk were also examined.
Results: Modest CRC risk reductions were observed per standard deviation increase in circulating linoleic acid (ORLA=0.96; 95% CI=0.93-0.98; p=5.2x10-4), α-linolenic acid (ORALA=0.95; 95% CI=0.92-0.97; p=5.4x10-5); whereas modest increased risks were observed for arachidonic acid (ORAA=1.06; 95% CI=1.03-1.08; p=3.3x10-5), eicosapentaenoic (OREPA=1.04; 95% CI=1.01-1.07; p=2.5x10-3), and docosapentaenoic acids (ORDPA=1.03; 95% CI=1.01-1.06; p=1.2x10-2. Each of these effects were stronger among aspirin/NSAID non-users in the stratified analyses.
Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced CRC risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased CRC risk.
Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared CRC inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on CRC.
| Original language | English |
|---|---|
| Pages (from-to) | 860–70 |
| Number of pages | 11 |
| Journal | Cancer Epidemiology, Biomarkers and Prevention |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Apr 2020 |
Access to Document
- Full-text PDF (accepted author manuscript)
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Association for Cancer Research at https://cebp.aacrjournals.org/content/29/4/860. Please refer to any applicable terms of use of the publisher.
- Supplementary information PDF 1
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Association for Cancer Research at https://cebp.aacrjournals.org/content/29/4/860. Please refer to any applicable terms of use of the publisher.
- Supplementary information PDF 2
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Association for Cancer Research at https://cebp.aacrjournals.org/content/29/4/860. Please refer to any applicable terms of use of the publisher.