Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma |
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| Authors: | Mark P. Purdue Patricia Hartge Scott Davis James R. Cerhan Joanne S. Colt Wendy Cozen Richard K. Severson Yan Li Stephen J. Chanock Nathaniel Rothman Sophia S. Wang |
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| Affiliation: | (1) Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8009, Rockville, MD 20892, USA;(2) Department of Health and Human Services, National Institutes of Health, Rockville, MD, USA;(3) Program in Epidemiology, Fred Hutchinson Cancer Research Center and Department of Epidemiology, University of Washington, Seattle, WA, USA;(4) Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA;(5) Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, CA, USA;(6) Department of Family Medicine and Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA;(7) Department of Health and Human Services, NCI Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Gaithersburg, MD, USA |
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| Abstract: | Objective Recent findings suggest that ultraviolet (UV) radiation exposure may reduce risk of developing non-Hodgkin lymphoma (NHL), but the biologic basis for this relationship remains unclear. We analyzed data from our US population-based case–control study of NHL to investigate whether our previously reported inverse association with sun exposure was dependent upon variants in the vitamin D receptor gene (IVS10 + 283G > A (BsmI), Ex11 + 32T > C (TaqI)), and genes linked to UV-induced immune modulation (IL4, IL10, IL12A, IL12B, TNF). Methods UV exposure data was collected from an in-person interview with 551 cases and 462 controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) for sun exposure measures for joint variant-exposure effects. Results The association with NHL risk for time in the midday sun within the last decade was dependent upon Ex11 + 32 T > C genotype. Compared to TT carriers who reported < 7 h/week of sun exposure, CC subjects with < 7 h/week of sun exposure had an increased risk of NHL (OR = 1.9, 95% CI 0.8–4.4, Pinteraction = 0.16), while the relative risks for other CC carriers approached unity with increasing level of sun exposure. This pattern of effects was especially apparent for follicular lymphoma (for CC genotype and < 7 h/week of exposure: OR 6.3, 95% CI 1.9–22, Pinteraction = 0.004), and was consistently observed across measures of reported sun exposure for different periods of life. As IVS10 + 283G > A is correlated with Ex11 + 32T > C in our population (r 2 = 0.95), results were equivalent for those with the IVS10 + 283 AA genotype. No evidence of interaction with cytokine gene variants was observed. Conclusions Our results suggest that the inverse association between UV exposure and NHL risk may be mediated by the vitamin D pathway. Further investigation of this finding in other studies is warranted. The U.S. Government's right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged. |
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| Keywords: | Non-Hodgkin lymphoma Vitamin D Polymorphism Genetic Sunlight |
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