A Prospective Analysis of Blood Donation History and Incidence of Non-Hodgkin Lymphoma
Authors: Ishii Kazusa , Birmann Brenda M. , Zhang Xuehong , Giovannucci Edward , Bertrand Kimberly A. 
Published: October 2019

Abstract
Background: The incidence rate of non-Hodgkin lymphoma (NHL) has more than doubled over the last few decades, but the reason for this increase has been largely unexplained. The long-term effect of blood donation on cancer incidence is not well investigated despite its potentially large impact on the population. Immune deficiency is associated with increased risk of NHL. Blood donation may influence subsequent NHL development via temporary immune system alterations following blood donation, which have been demonstrated in several human studies. A large nested case-control study within a cohort of blood donors in Sweden and Denmark showed an increased odds ratio (OR) of NHL among frequent plasma donors comparing to non-donors (OR 2.14, 95% confidence interval (CI) 1.22-3.74) [Edgren G et al., 2008]. Results of this and other studies have been difficult to interpret because of the possible influence of healthy donor effects or different baseline characteristics among blood donors compared to general population. To test the hypothesis that frequent blood donation is associated with an increased risk of NHL and its most common histologic subtypes in a general, non-immune compromised population, we conducted a prospective study in the Health Professional Follow-up Study (HPFS) cohort.
Methods: We followed 36,580 men in the HPFS cohort, who in 1992 had no prior diagnosis of cancer and provided information on frequency of blood donation in the past 30 years. Throughout follow-up of the HPFS cohort, participants completed questionnaires about lifestyle and medical history every two years. Non-respondents were followed through the National Death Index. Identified diagnoses of cancer were confirmed by medical record review. The present analysis included all confirmed incident diagnoses of NHL through January 2008. Person-time accrued for each participant from January 1992 to the earliest among dates of NHL diagnosis, death, or January 2008. Cox proportional hazards regression was used to calculate hazards ratios (HR) and 95% CIs for the risk of all NHL and major NHL histologic subtypes associated with number of blood donations (1-5, 6-9, 10-19, or >20, vs. none), stratifying by age in months and follow-up cycle. Potential confounding by putative NHL risk factors (i.e. smoking, alcohol, BMI, height, physical activity, race) was evaluated by including these factors in multivariable models.
Results: During 482,008 person-years of follow-up, 484 incident cases of NHL were confirmed. Participant characteristics were similar at baseline among blood donors and non-donors with respect to age, race, and selected lifestyle factors. In the age-adjusted model, there was no significant association between blood donation frequency and incidence of NHL (HR 1.12, 95% CI 0.82-1.55, comparing >20 donations vs. 0 donations over 30 years, p for trend = 0.44) or of any major NHL subtypes. Adjustment for potential confounders did not notably change the effect estimates for all NHL or any NHL subtypes.
Conclusion: In this prospective study, there was no evidence that frequent blood donation is associated with incidence of all NHL or any major subtypes.

Disclosures
No relevant conflicts of interest to declare.