Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma.
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.
Purdue
Mark P
MP
Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8009, Rockville, MD 20892, USA. purduem@mail.nih.gov
Hartge
Patricia
P
Davis
Scott
S
Cerhan
James R
JR
Colt
Joanne S
JS
Cozen
Wendy
W
Severson
Richard K
RK
Li
Yan
Y
Chanock
Stephen J
SJ
Rothman
Nathaniel
N
Wang
Sophia S
SS
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016001:Confidence Intervals; D005006:Ethnicity / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008224:Lymphoma, Follicular / Q000453:epidemiology / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D018426:SEER Program; D013472:Sunlight; D011795:Surveys and Questionnaires; D013997:Time Factors; D014466:Ultraviolet Rays; D014481:United States / Q000453:epidemiology
D018167:Receptors, Calcitriol