Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.
Moore A., Kane E., Teras LR., Machiela MJ., Arias J., Panagiotou OA., Monnereau A., Doo NW., Wang Z., Slager SL., Vermeulen RCH., Vajdic CM., Smedby KE., Spinelli JJ., Vijai J., Giles GG., Link BK., Arslan AA., Nieters A., Bracci PM., Camp NJ., Salles G., Cozen W., Hjalgrim H., De Vivo I., Adami H-O., Albanes D., Becker N., Benavente Y., Bisanzi S., Boffetta P., Brennan P., Brooks-Wilson AR., Canzian F., Clavel J., Conde L., Cox DG., Curtin K., Foretova L., Ghesquières H., Glimelius B., Habermann TM., Hofmann JN., Lan Q., Liebow M., Lincoln A., Maynadie M., McKay J., Melbye M., Miligi L., Milne RL., Molina TJ., Morton LM., North KE., Offit K., Padoan M., Piro S., Patel AV., Purdue MP., Ravichandran V., Riboli E., Severson RK., Southey MC., Staines A., Tinker LF., Travis RC., Wang SS., Weiderpass E., Weinstein S., Zheng T., Chanock SJ., Rothman N., Birmann BM., Cerhan JR., Berndt SI.
Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05-1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (ORper SD = 1.12, 95% CI: 1.02-1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.