A prospective analysis of red blood cell membrane polyunsaturated fatty acid levels and risk of non-Hodgkin lymphoma

Abstract

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses’ Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03–1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23–4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

Keywords:

• Red blood cell membrane fatty acids
• polyunsaturated fatty acids
• non-Hodgkin lymphoma
• epidemiology
• prospective
• etiology

Acknowledgments

The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming. The authors assume full responsibility for analyses and interpretation of these data. The authors would also like to thank the participants and staff of the NHS and HPFS for their dedication and contribution to the research and Jeremy Furtado for measurement of the RBC membrane fatty acid levels.

Ethical approval

This human subjects research was performed in accordance with the Declaration of Helsinki. The present study protocol was approved by and conducted in accordance with the ethical standards of the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating cancer registries as required. Nurses’ Health Study and Health Professionals Follow-up Study participant informed consent was implied by return of the baseline questionnaire; blood subcohort participants provided written informed consent at time of blood collection. This manuscript does not contain any individual person’s data in any form.

Author contributions

BMB designed the research; HC provided data; AVAK and Y-HC analyzed data; AVAK and BMB interpreted the data and wrote the paper; KAB, SZ, MME, BAR, SC, ELG and JEG helped with data interpretation and provided critical scientific input. All the authors critically reviewed the manuscript for important intellectual content and gave final approval; BMB and AVAK had primary responsibility for the final contents.

Disclosure statement

SC is presently an employee at AbbVie, in which capacity she receives stock/stock options; SZ is presently an employee and holds restricted share units of Johnson & Johnson; neither SC nor SZ had competing interests or conflicts at the time the project was designed, funded and initiated. The remaining authors declare no potential competing interests or conflicts of interest. No potential conflict of interest was reported by the author(s).

Data availability statement

Data described in the manuscript, code book, and analytic code will not be made available because of participant confidentiality and privacy concerns. Further information, including the procedures to obtain and access data from the Nurses’ Health Studies and Health Professionals Follow-up Study, is described at https://www.nurseshealthstudy.org/researchers (contact email: [email protected]) and https://sites.sph.harvard.edu/hpfs/for-collaborators/.

Additional information

Funding

This work was supported by the [American Cancer Society] under [Research Scholar Grant RSG-11-020-01-CNE], by grants from the [National Institutes of Health] under grants [UM1 CA186107]; [P01 CA87969]; [R01 CA49449]; [U01 CA167552]; [R01 CA149445]; [R01 CA09812]; [U54 CA155626]; [P30 DK46200]; [KL2 TR001455 (to MME)], and [T32 CA009001 (to AVAK)] and the American Heart Association [grant 834106 to Y-HC].