Plasma fatty acids, genetic risk, and incident pancreatic cancer: A prospective cohort study

Evidence regarding the association between circulating levels of fatty acids (FAs) and the risk of pancreatic cancer (PC) remains limited, and the effect modification by genetic risk status remains unclear.

A cohort study was conducted involving 249,165 cancer-free participants from the UK Biobank, with measurements of plasma FAs, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). Cox regression models were employed to assess PC risk according to the quartiles of specific FAs (percentages in total FAs). Interactions between plasma FAs and genetic risk for PC were further evaluated.

Over an average 12.8 years follow-up, 776 PC cases occurred. The incidence of PC was 24.95 per 100,000 person-years. After multivariable adjustment, SFAs% were positively associated with PC risk (HR _{Q4 vs. Q1}, 1.42; 95 % CI, 1.15-1.76; P-trend = 0.002). In contrast, PUFAs%, particularly n-3 PUFAs%, were inversely associated with the risk of PC (P-trend values < 0.05). MUFAs% were not associated with PC risk. The association for SFAs% appeared to be stronger among individuals with a higher genetic risk for PC (HR _{Q4 vs. Q1} = 1.63, 95 % CI: 1.19-2.23) than among those with a lower genetic risk (HR _{Q4 vs. Q1} = 1.23, 95 % CI: 0.75-2.01), although the interaction was not significant (P-interaction = 0.18). As a result, participants with both higher SFAs% and a higher genetic risk had a particularly higher risk for PC (HR = 3.60; 95 % CI, 2.38-5.45), when comparing those with lower levels of both exposures.

Increasing plasma SFAs were associated with a higher risk of PC, whereas plasma PUFAs especially n-3 PUFAs were inversely associated with PC risk. The potential interaction between SFAs and genetic risk for PC warrants further investigation.