Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma

Cancer Causes Control. 2007 Nov;18(9):989-99. doi: 10.1007/s10552-007-9039-z. Epub 2007 Jul 25.

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, 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Confidence Intervals
  • Ethnic Groups / statistics & numerical data
  • Female
  • Humans
  • Interviews as Topic
  • Lymphoma, Follicular / epidemiology
  • Lymphoma, Follicular / genetics
  • Lymphoma, Non-Hodgkin / epidemiology
  • Lymphoma, Non-Hodgkin / genetics*
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Risk Factors
  • SEER Program
  • Sunlight*
  • Surveys and Questionnaires
  • Time Factors
  • Ultraviolet Rays
  • United States / epidemiology

Substances

  • Receptors, Calcitriol