Prospective study on the association between 36 human blood cell traits and pan-cancer outcomes: a mendelian randomization analysis.

Abstract

Background: Research on the link between blood cell traits and cancer risk has gained significant attention. Traditional epidemiological and cell biology studies, have identified correlations between blood traits and cancer risks. These findings are important as they suggest potential risk factors and biological mechanisms. However, these studies often can't confirm causality, pointing to the need for further investigation to understand these relationships better.

Methods: Mendelian randomization (MR), utilizing single-nucleotide polymorphisms as instrumental variables, was employed to investigate blood cell trait causal effects on cancer risk. Thirty-six blood cell traits were analyzed, and their impact on 28 major cancer outcomes was assessed using data from the FinnGen cohort, with eight major cancer outcomes and 22 cancer subsets. Furthermore, 1,008 MR analyses were conducted, incorporating sensitivity analyses (weighted median, MR-Egger, and MR-PRESSO) to address potential pleiotropy and heterogeneity.

Results: The analysis (data from 173,480 individuals primarily of European descent) revealed significant results. An increase in eosinophil count was associated with a reduced risk of colorectal malignancies (OR = 0.7702 per 1 SD higher level, 95% CI = 0.6852 to 0.8658; P = 1.22E-05). Similarly, an increase in total eosinophil and basophil count was linked to a decreased risk of colorectal malignancies (OR = 0.7798 per 1 SD higher level, 95% CI = 0.6904 to 0.8808; P = 6.30E-05). Elevated hematocrit (HCT) levels were associated with a reduced risk of ovarian cancer (OR = 0.5857 per 1 SD higher level, 95% CI = 0.4443 to 0.7721; P = 1.47E-04). No significant heterogeneity or horizontal pleiotropy was observed.

Conclusions: Our study highlights the complex and context-dependent roles of blood cell traits in cancers.