Fatty acid and colorectal and bladder cancer risk

Dietary fat composition may play an important role in cancer development, yet the effects of specific fatty acids on colorectal cancer (CRC) and bladder cancer (BC) remain unclear, particularly in non-Western populations. This multicenter case-control study, conducted between 2017 and 2020 within the IROPICAN project across seven Iranian provinces, examined associations between dietary and plasma fatty acids and the risk of CRC and BC. Incident CRC and BC cases were pathologically confirmed and compared with cancer-free controls. Usual dietary intake in the year preceding diagnosis or interview was assessed using a validated food frequency questionnaire, and fatty acid intakes were estimated using Iranian-adapted food composition tables. In a nested CRC sub-study, plasma phospholipid fatty acids were measured by gas chromatography. Multivariable logistic regression, principal component analysis, and LASSO regression were applied to evaluate associations and identify key predictors. Among 865 CRC cases, 717 BC cases, and over 6,500 controls, higher intakes of total fat, cholesterol, saturated fatty acids, and industrial trans fatty acids were associated with increased CRC risk, while higher intake of heptanoic acid and ruminant trans fatty acids showed inverse associations. Elevated dietary palmitoleic acid and elaidic acid were strongly linked to higher CRC risk. Plasma analyses supported these findings, with higher levels of saturated fatty acids, industrial trans fats, long-chain n-6 polyunsaturated fatty acids, and a higher n-6/n-3 ratio associated with increased CRC risk, whereas omega-3 fatty acids were inversely related. In BC analyses, a fat-dominant dietary pattern was associated with increased risk, while higher monounsaturated and omega-3 fatty acid intake, particularly among women, was protective. Overall, these results underscore the importance of dietary fat quality in reducing CRC and BC risk.