Hormonal and reproductive factors and subsequent risk of haematological malignancies: findings from the UK Biobank

Background: Haematological malignancies (HM) are male dominant; the reasons for which remain unknown. Immunomodulatory exposures have been reported to increase HM risk leading to speculation that female sex hormones which exert immunomodulatory effects may protect against HM development in women. We aimed to investigate the association between hormonal and reproductive factors and subsequent risk of HM in a large cohort of males and females within the United Kingdom (UK). Methods: The UK Biobank is a large prospective cohort study of 502,628 men and women aged 40 to 69 years of age recruited during the period 2006-2010. Information on hormonal and reproductive factors was obtained from participant’s baseline assessments. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models, adjusting for age, socioeconomic status, body mass index, waist-to-hip ratio, education, smoking status and alcohol consumption. Results: A total of 2,174 HM (n= 1,162 lymphoma, n=606 leukaemia and n=406 plasma cell neoplasms) were identified during the study period. In preliminary analysis, a significant increased risk of lymphoma among females was associated with prior bilateral oophorectomy and ever use of hormone replace therapy (HRT) whereas reduced risks were observed for older age of menopause (51-54 years vs