Prospective Analysis Of Statin Use and Risk Of Non-Hodgkin’s Lymphoma In The Women’s Health Initiative Cohort
Authors: Desai Pinkal , Wallace Robert , Anderson Matthew , Alqwasmi Abdel , Howard Barbara V. , Wu Chunyuan , Safford Monica , Martin Lisa W. , Schlecht Nicolas , Liu Simin , Cetnar Jeremy , Cirillo Dominic , Jay Allison , Manson JoAnn E. , Simon Michael S. 
Published: October 2019

Abstract

Introduction
HMG CoA reductase inhibitors (statins) are a class of cholesterol lowering drugs that affect many intracellular pathways and have implications for cancer chemo prevention. Statins have been shown to induce a phosphoprotein signature that shuts MYC activation and also have anti-inflammatory activity that may impact the risk of Non-Hodgkin’s lymphoma (NHL). Results from observational studies on the relationship between statin use and NHL are conflicting. We analyzed data from the Women’s Health Initiative (WHI) to assess the relationship between statins and the risk of NHL.

Methods
The study population included 161,563 post-menopausal women ages 50-79 years. Women with incident NHL were identified over an average of 10.8 (SD +3.3) years of follow-up. Information on statin use was collected at study entry and at years 1, 3, 6 and 9. Statins were classified as lipophilic (simvastatin, lovastatin, fluvastatin) or hydrophilic (pravastatin, atorvastatin) by potency (low, medium, high) and by duration of use. Self and interviewer-administered questionnaires were used to collect information on other risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to evaluate the relationship between statin use and NHL risk as a time-dependent exposure. Multivariable models were stratified by WHI trial, extension study and age group and were adjusted for education, ethnicity, smoking, alcohol, body mass index, waist circumference, % energy from fat, hormone therapy use, physical activity, current medical provider and history of lupus and rheumatoid arthritis. A separate analysis was performed for individual NHL subtypes: Diffuse Large B cell Lymphoma (DLBCL) (n=228), follicular lymphoma (n=169) and Small Lymphocytic Lymphoma/Chronic Lymphocytic Lymphoma (SLL/CLL) (n=74).All statistical tests were two-sided.

Results
Statins were used at baseline by 12,243 women (7.5%), 8266 of whom used lipophilic agents. The multivariable adjusted HR of overall statin use and risk of NHL was 0.66 (95% CI: 0.48-0.90). Hydrophilic statin use was associated with a significantly lower risk of developing NHL (HR 0.47, 95% C.I. 0.27-0.81); HR for pravastatin 0.46 (95% C.I. 0.20-1.02) and for atorvastatin 0.39 (95% C.I. 0.124-1.20). Lipophilic statins were not associated with NHL risk (HR 0.85, 95% C.I. 0.58-1.24). Among NHL subtypes, statin use was associated with a lower risk of DLBCL (HR 0.49, 95% C.I. 0.25-0.96) however there was no association with follicular lymphoma (HR 0.92, 95% C.I. 0.49-1.70) or CLL/SLL (HR 1.18, 95% C.I. 0.50-2.75).

Conclusion
Prior use of statins was associated with a lower overall risk of NHL attributable to a lower risk of DLBCL in the WHI cohort. This effect was largely seen among users of hydrophilic statins.

Disclosures:
Safford: Amgen: Research Funding.