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2007: Purdue Mark P; Hartge Patricia; Davis Scott; Cerhan James R; Colt Joanne S; Cozen Wendy; Severson Richard K; Li Yan; Chanock Stephen J; Rothman Nathaniel; Wang Sophia S
Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma.
Cancer causes & control : CCC 2007;18(9):989-99.
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, P(interaction) = 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, P(interaction) = 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.

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