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Background: Previous reports suggest that blood donors have a lower mortality risk, which may partially reflect the "healthy donor effect" (HDE). HDE arises in donors due to selection bias and confounding if not appropriately addressed., Study Design and Methods: Using the Sax Institute's 45 and Up Study data linked with blood donation history, we used a "5-year exposure window" method to select donors into regular high-frequency whole blood (WB)donors (at least two donations per exposure year) and low-frequency donors (remaining donors) with an active donation career of 5 years. To further reduce the confounding, we used statistical approaches like the inverse probability weighted (IPW) marginal structural model and the doubly robust targeted minimum loss-based estimator (TMLE), which incorporated machine learning algorithms and time-varying analyses., Results: We selected 4750 (64.7%) low-frequency and 2588 (35.3%) high-frequency donors in the analyses. A total of 69 (1.5%) from the low-frequency and 45 (1.7%) donors from the regular high-frequency group died during the 7-year follow-up period. We did not find any statistically significant association between regular high-frequency blood donation and mortality (IPW RR = 0.98 95% CI 0.68, 1.28). TMLE model also showed similar results to IPW (RR = 0.97 95% CI 0.80, 1.16). Time-varying TMLE did not find any significant association between high-frequency donation and all-cause mortality either (RR = 0.98 95% 0.74, 1.29)., Conclusions: We did not find a significant association between regular high-frequency WB donation and all-cause mortality when appropriate methods were employed to minimize the HDE., (© 2024 AABB.)

Background and Objectives: Several studies have suggested that blood donors have lower risk of gastrointestinal and breast cancers, whereas some have indicated an increased risk of haematological cancers. We examined these associations by appropriately adjusting the 'healthy donor effect' (HDE)., Materials and Methods: We examined the risk of gastrointestinal/colorectal, breast and haematological cancers in regular high-frequency whole blood (WB) donors using the Sax Institute's 45 and Up Study data linked with blood donation and other health-related data. We calculated 5-year cancer risks, risk differences and risk ratios. To mitigate HDE, we used 5-year qualification period to select the exposure groups, and applied statistical adjustments using inverse probability weighting, along with other advanced doubly robust g-methods., Results: We identified 2867 (42.4%) as regular high-frequency and 3888 (57.6%) as low-frequency donors. The inverse probability weighted 5-year risk difference between high and low-frequency donors for gastrointestinal/colorectal cancer was 0.2% (95% CI, -0.1% to 0.5%) with a risk ratio of 1.25 (0.83-1.68). For breast cancer, the risk difference was -0.2% (-0.9% to 0.4%), with a risk ratio of 0.87 (0.48-1.26). Regarding haematological cancers, the risk difference was 0.0% (-0.3% to 0.5%) with a risk ratio of 0.97 (0.55-1.40). Our doubly robust estimators targeted minimum loss-based estimator (TMLE) and sequentially doubly robust (SDR) estimator, yielded similar results, but none of the findings were statistically significant., Conclusion: After applying methods to mitigate the HDE, we did not find any statistically significant differences in the risk of gastrointestinal/colorectal, breast and haematological cancers between regular high-frequency and low-frequency WB donors., (© 2024 The Author(s). Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)