Vitamin D Receptor Genotypes, Ultraviolet Radiation Exposure, and Risk of Non-Hodgkin Lymphoma

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BlankVitamin D Receptor Genotypes, Ultraviolet Radiation Exposure, and Risk of

Non-Hodgkin Lymphoma

1.. Karin Ekström Smedby*,

2.. Eloranta,

3.. a Duvefelt,

4.. Mads Melbye,

5.. Humphreys,

6.. Henrik Hjalgrim and

7.. Ellen T. Chang

1.. *Correspondence to Dr. Karin Ekström Smedby, Department of Medicine Solna,

Clinical Epidemiology Unit, Karolinska Institutet and Karolinska University

Hospital, SE-171 76 Stockholm, Sweden (e-mail: karin.ekstrom.smedby@...).

a.. Received April 9, 2010.

b.. Accepted September 2, 2010.

Abstract

Ultraviolet radiation (UVR) exposure may influence risk of non-Hodgkin lymphoma

(NHL) through vitamin D, with antineoplastic effects mediated through the

vitamin D receptor (VDR). To explore the role of vitamin D in NHL risk and the

potential interaction with UVR, the authors genotyped 10 VDR polymorphisms in

2,448 NHL patients and 1,981 controls from Denmark and Sweden who were recruited

in 1999–2002. Odds ratios and 95% confidence intervals were computed with

logistic regression. P values were 2-sided. Most VDR variants (e.g.,

rs731236/TaqI, rs15444410/BsmI) were not associated with overall risk of NHL,

but there was some evidence of a positive association between rs4760655 and

follicular lymphoma risk (nominal Ptrend = 0.004, corrected Ptrend = 0.24).

There was no support for an effect of interaction between VDR variants and UVR

exposure on risk of overall NHL or B-cell lymphoma subtypes. However, there was

some evidence that rs731236 altered associations between UVR and T-cell NHL

risk; while increasing UVR frequency lowered T-cell NHL risk among rs731236 TT

carriers, an elevated risk was observed among rs731236 CC carriers (nominal

Pinteraction = 0.008, corrected Pinteraction = 0.12). VDR does not appear to

harbor major determinants of NHL risk, except perhaps for follicular lymphoma.

Possible heterogeneity in effects of UVR exposure on T-cell lymphoma risk by VDR

rs731236 genotype merits further investigation.