A Prospective Analysis of Red Blood Cell Trans Fatty Acid Levels and Risk of Non-Hodgkin Lymphoma

To confirm previous reports of increased non-Hodgkin lymphoma (NHL) risk with higher intake of dietary trans fatty acids (TFA), we conducted the first prospective study of pre-diagnosis red blood cell (RBC) TFA levels and risk of NHL and common NHL histologic subtypes (diffuse large-B cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic lymphoma/small lymphocytic leukemia, other B-cell NHL, T-cell NHL). Methods: We conducted a nested case-control study in Nurses9 Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) participants with archived RBC specimens and no history of cancer at sample collection (NHS: 1989–90; HPFS: 1994–5). We confirmed 583 NHL cases (332 women in NHS, 251 men in HPFS) and matched 583 controls by cohort (sex), age, race/ethnicity and blood draw date/time. We analyzed RBC TFAs using gas-liquid chromatography; individual TFA levels were expressed as a percentage of total fatty acids. We used unconditional logistic regression, adjusted for the matching factors, to estimate odds ratios (OR) and 95% confidence intervals (CI) for overall NHL risk per 1 standard deviation (SD) unit increase in TFA level. We fitted multivariate polytomous logistic regression models to assess associations for the specific subtypes listed above. Results: Total and individual RBC TFAs were not associated with overall NHL risk or risk of most histologic subtypes. However, we observed a positive association of total RBC TFA with DLBCL risk ( n = 86 cases; OR [95% CI] per 1 SD: 1.29 [1.02, 1.64]), driven primarily by 18:1 TFAs (1.35 [1.07, 1.72]). Among 18:1 TFA isomers, we found a positive association for trans 18:1 n-9 (elaidic acid; 1.33 [1.05, 1.68]) but not for other isomers. Conclusions: We observed significant positive associations for RBC TFA levels with DLBCL risk. These findings are consistent with published studies of self-reported TFA intake; further, previous studies have shown that TFA levels – particularly trans 18:1n-9, which is industrially-derived – are positively correlated with biomarkers of inflammation and immune activation, supporting the biologic plausibility of our findings. Food industry and public health measures to diminish TFA intake may help to reduce risk of NHL, and particularly of DLBCL.