Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian...

Area of Science:

• Genetics and Epidemiology
• Cancer Research
• Metabolic Health

Background:

• Obesity is a growing global health concern linked to various cancers.
• The relationship between obesity and non-Hodgkin lymphoma (NHL) requires further clarification.
• Previous studies have shown inconsistent associations between adiposity and NHL risk.

Purpose of the Study:

• To investigate the association between genetically determined adiposity and specific NHL subtypes.
• To determine if genetic predisposition to higher BMI or altered body fat distribution increases DLBCL risk.
• To differentiate the impact of adiposity on DLBCL versus other common NHLs.

Main Methods:

• Utilized genome-wide association studies (GWAS) data from European ancestry (10,629 cases, 9505 controls).
• Constructed polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and WHR adjusted for BMI (WHRadjBMI).
• Employed Mendelian randomization analyses to assess causal relationships.

Main Results:

• A significant positive association was found between genetically determined higher BMI and increased risk of diffuse large B-cell lymphoma (DLBCL).
• Mendelian randomization analyses corroborated the link between genetically predicted BMI and DLBCL risk.
• No significant associations were observed between genetically determined adiposity measures and follicular lymphoma, chronic lymphocytic leukemia, or marginal zone lymphoma.

Conclusions:

• Genetically determined higher BMI is a risk factor for developing DLBCL.
• Increased adiposity, particularly higher BMI, contributes to DLBCL pathogenesis.
• The findings highlight a specific link between BMI and DLBCL, distinct from other NHL subtypes.