The Association between Hemoglobin Level and Cancer Incidence, Mortality and Inflammatory Biomarkers in Post-Menopausal Women

Abstract

Background: Knowledge regarding the associations of (i) hemoglobin level (Hb) prior to cancer diagnosis and cancer mortality (ii) the full range of Hb and cancer incidence and (iii) baseline inflammatory/other biomarkers and Hb in older populations is limited. The present study examined the associations of anemia status/Hb with cancer incidence and mortality, as well as the association with inflammatory biomarker levels in post-menopausal women. Methods: Anemia was defined as Hb <1 2 g/dl, while high Hb was defined as Hb >= 15 g/dl, or >= 16 g/dl. Associations were determined in three Women's Health Initiative Study sub-populations. The association between anemia/Hb with cancer mortality was determined in women without (N=21,021) or with (N=2,976) cancer history who had cancers on follow-up. The cross-sectional association of biomarkers and anemia/Hb was determined on 1,001 women with these available data. Finally, the association between anemia/Hb with cancer incidence was determined in women enrolled in the Observational Study/Clinical Trial who did not have a history of cancer/extreme energy intakes/missing follow-up time (N=140,269). Results: Anemia was associated with a 21% higher hazard of total cancer death in participants with, and a 55% greater hazard in participants without cancer history. Anemic women with a history of cancer had twice the hazard of colorectal cancer death. C-reactive protein, TNF-alpha, TNF-beta and TNFR2 were significantly associated with anemia. IL-1 alpha and IL-10 were significantly associated with continuous Hb. Anemia was not associated with cancer incidence in the total population, but anemic African-American women had a reduced risk of any cancer incidence which was not observed in white women (p-interaction=0.03). Women with high Hb had an increased hazard of any (HR: 1.37; 95% CI: 1.17, 1.60) or breast cancer (HR: 1.42; 95% CI: 1.10, 1.84) incidence. Conclusions: Anemia determined prior to cancer diagnosis was associated with total and colorectal cancer death. High Hb was associated with increased risk of total cancer and breast cancer incidence. Anemia was associated with elevated levels of C-reactive protein, TNF-alpha, TNF-beta and TNFR2, while continuous Hb was associated with IL-1 alpha and IL-10. Further research is required to confirm associations and clarify causal mechanisms.