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Cancer Causes & Control
Published in: Cancer Causes & Control 7/2012

01-07-2012 | Original Paper

Early life sun exposure, vitamin D-related gene variants, and risk of non-Hodgkin lymphoma

Authors: Jennifer L. Kelly, Matthew T. Drake, Zachary S. Fredericksen, Yan W. Asmann, Mark Liebow, Tait D. Shanafelt, Andrew L. Feldman, Stephen M. Ansell, William R. Macon, Megan M. Herr, Alice H. Wang, Grzegorz S. Nowakowski, Timothy G. Call, Thomas M. Habermann, Susan L. Slager, Thomas E. Witzig, James R. Cerhan

Published in: Cancer Causes & Control | Issue 7/2012

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Abstract

Purpose

It has been hypothesized that vitamin D mediates the inverse relationship between sun exposure and non-Hodgkin lymphoma (NHL) risk reported in several recent studies. We evaluated the association of self-reported sun exposure at ages <13, 13–21, 22–40, and 41+ years and 19 single nucleotide polymorphisms (SNPs) from 4 candidate genes relevant to vitamin D metabolism (RXR, VDR , CYP24A1, CYP27B1) with NHL risk.

Methods

This analysis included 1,009 newly diagnosed NHL cases and 1,233 frequency-matched controls from an ongoing clinic-based study. Odds ratios (OR), 95 % confidence intervals (CI), and tests for trend were estimated using unconditional logistic regression.

Results

There was a significant decrease in NHL risk with increased sun exposure at ages 13–21 years (OR≥15 vs. ≤3 h/week = 0.68; 95 % CI, 0.43–1.08; p trend = 0.0025), which attenuated for older ages at exposure. We observed significant main effect associations for 3 SNPs in VDR and 1 SNP in CYP24A1: rs886441 (ORper-allele = 0.82; 95 % CI, 0.70–0.96; p = 0.016), rs3819545 (ORper-allele = 1.24; 95 % CI, 1.10–1.40; p = 0.00043), and rs2239186 (ORper-allele = 1.22; 95 % CI, 1.05–1.41; p = 0.0095) for VDR and rs2762939 (ORper-allele = 0.85; 95 % CI, 0.75–0.98; p = 0.023) for CYP24A1. Moreover, the effect of sun exposure at age 13–21 years on overall NHL risk appears to be modified by germline variation in VDR (rs4516035; p interaction = 0.0066). Exploratory analysis indicated potential heterogeneity of these associations by NHL subtype.

Conclusion

These results suggest that germline genetic variation in VDR, and therefore the vitamin D pathway, may mediate an association between early life sun exposure and NHL risk.
Literature
1.
2.
Alexander DD, Mink PJ, Adami HO, Chang ET, Cole P, Mandel JS, Trichopoulos D (2007) The non-Hodgkin lymphomas: a review of the epidemiologic literature. Int J Cancer 120(Suppl 12):1–39PubMedCrossRef
3.
Hartge P, Lim U, Freedman DM, Colt JS, Cerhan JR, Cozen W, Severson RK, Davis S (2006) Ultraviolet radiation, dietary vitamin D, and risk of non-Hodgkin lymphoma (United States). Cancer Causes Control 17(8):1045–1052PubMedCrossRef
4.
Soni LK, Hou L, Gapstur SM, Evens AM, Weisenburger DD, Chiu BC (2007) Sun exposure and non-Hodgkin lymphoma: a population-based, case-control study. Eur J Cancer 43(16):2388–2395PubMedCrossRef
5.
Weihkopf T, Becker N, Nieters A, Mester B, Deeg E, Elsner G, Blettner M, Seidler A (2007) Sun exposure and malignant lymphoma: a population-based case-control study in Germany. Int J Cancer 120(11):2445–2451PubMedCrossRef
6.
Hughes AM, Armstrong BK, Vajdic CM, Turner J, Grulich AE, Fritschi L, Milliken S, Kaldor J, Benke G, Kricker A (2004) Sun exposure may protect against non-Hodgkin lymphoma: a case-control study. Int J Cancer 112(5):865–871PubMedCrossRef
7.
Smedby KE, Hjalgrim H, Melbye M, Torrang A, Rostgaard K, Munksgaard L, Adami J, Hansen M, Porwit-MacDonald A, Jensen BA, Roos G, Pedersen BB, Sundstrom C, Glimelius B, Adami HO (2005) Ultraviolet radiation exposure and risk of malignant lymphomas. J Natl Cancer Inst 97(3):199–209PubMedCrossRef
8.
Chang ET, Canchola AJ, Cockburn M, Lu Y, Wang SS, Bernstein L, Clarke CA, Horn-Ross PL (2011) Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study. Blood 118(6):1591–1599PubMedCrossRef
9.
Zhang Y, Holford TR, Leaderer B, Boyle P, Zhu Y, Wang R, Zou K, Zhang B, Wise JP Sr, Qin Q, Kilfoy B, Han J, Zheng T (2007) Ultraviolet radiation exposure and risk of non-Hodgkin’s lymphoma. Am J Epidemiol 165(11):1255–1264PubMedCrossRef
10.
Veierod MB, Smedby KE, Lund E, Adami HO, Weiderpass E (2010) Pigmentary characteristics, UV radiation exposure, and risk of non-Hodgkin lymphoma: a prospective study among Scandinavian women. Cancer Epidemiol Biomarkers Prev 19(6):1569–1576PubMedCrossRef
11.
Freedman DM, Kimlin MG, Hoffbeck RW, Alexander BH, Linet MS (2010) Multiple indicators of ambient and personal ultraviolet radiation exposure and risk of non-Hodgkin lymphoma (United States). J Photochem Photobiol, B 101(3):321–325CrossRef
12.
Bertrand KA, Chang ET, Abel GA, Zhang SM, Spiegelman D, Qureshi AA, Laden F (2011) Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses’ Health Study. Cancer Causes Control 22(12):1731–1741PubMedCrossRef
13.
Kricker A, Armstrong BK, Hughes AM, Goumas C, Smedby KE, Zheng T, Spinelli JJ, De Sanjose S, Hartge P, Melbye M, Willett EV, Becker N, Chiu BC, Cerhan JR, Maynadie M, Staines A, Cocco P, Boffeta P (2008) Personal sun exposure and risk of non Hodgkin lymphoma: a pooled analysis from the Interlymph Consortium. Int J Cancer 122(1):144–154PubMedCrossRef
14.
Holick MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80(6 Suppl):1678S–1688SPubMed
15.
Kelly JL, Friedberg JW, Calvi LM, van Wijngaarden E, Fisher S (2009) Vitamin D and non-Hodgkin lymphoma risk in adults: a review. Cancer Invest 27(9):942–951PubMedCrossRef
16.
Rhee HV, Coebergh JW, Vries ED (2009) Sunlight, vitamin D and the prevention of cancer: a systematic review of epidemiological studies. Eur J Cancer Prev 18:458–475PubMedCrossRef
17.
Raimondi S, Johansson H, Maisonneuve P, Gandini S (2009) Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 30(7):1170–1180PubMedCrossRef
18.
Purdue MP, Lan Q, Kricker A, Vajdic CM, Rothman N, Armstrong BK (2007) Vitamin D receptor gene polymorphisms and risk of non-Hodgkin’s lymphoma. Haematologica 92(8):1145–1146PubMedCrossRef
19.
Purdue MP, Hartge P, Davis S, Cerhan JR, Colt JS, Cozen W, Severson RK, Li Y, Chanock SJ, Rothman N, Wang SS (2007) Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma. Cancer Causes Control 18(9):989–999PubMedCrossRef
20.
Smedby KE, Eloranta S, Duvefelt K, Melbye M, Humphreys K, Hjalgrim H, Chang ET (2011) Vitamin D receptor genotypes, ultraviolet radiation exposure, and risk of non-Hodgkin lymphoma. Am J Epidemiol 173(1):48–54PubMedCrossRef
21.
Samuel S, Sitrin MD (2008) Vitamin D’s role in cell proliferation and differentiation. Nutr Rev 66(10 Suppl 2):S116–S124PubMedCrossRef
22.
Bikle DD (2010) Vitamin D: newly discovered actions require reconsideration of physiologic requirements. Trends Endocrinol Metab 21(6):375–384PubMedCrossRef
23.
24.
Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, Hewison M (2001) Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab 86(2):888–894PubMedCrossRef
25.
Hickish T, Cunningham D, Colston K, Millar BC, Sandle J, Mackay AG, Soukop M, Sloane J (1993) The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma. Br J Cancer 68(4):668–672PubMedCrossRef
26.
Cerhan JR, Ansell SM, Fredericksen ZS, Kay NE, Liebow M, Call TG, Dogan A, Cunningham JM, Wang AH, Liu-Mares W, Macon WR, Jelinek D, Witzig TE, Habermann TM, Slager SL (2007) Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma. Blood 110(13):4455–4463PubMedCrossRef
27.
Cerhan JR, Fredericksen ZS, Wang AH, Habermann TM, Kay NE, Macon WR, Cunningham JM, Shanafelt TD, Ansell SM, Call TG, Witzig TE, Slager SL, Liebow M (2011) Design and validity of a clinic-based case-control study on the molecular epidemiology of lymphoma. Int J Mol Epidemiol Genet 2(2):95–113PubMed
28.
Jaffe ES, Harris N, Stein H, Vardiman J (2001) World Health Organization classification of tumours pathology and genetics, tumors of hematopoietic and lymphoid tissues. IARC Press, Lyon
29.
Holick CN, Stanford JL, Kwon EM, Ostrander EA, Nejentsev S, Peters U (2007) Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer. Cancer Epidemiol Biomarkers Prev 16(10):1990–1999PubMedCrossRef
30.
McCullough ML, Bostick RM, Mayo TL (2009) Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer. Annu Rev Nutr 29:111–132PubMedCrossRef
31.
Oliphant A, Barker DL, Stuelpnagel JR, Chee MS (2002) BeadArray technology: enabling an accurate, cost-effective approach to high-throughput genotyping. Biotechniques Suppl:56–58 (60–51)
32.
Hosmer DW, Lemeshow S (2000) Applied logistic regression, 2nd edn. Wiley, New YorkCrossRef
33.
Pan SY, Morrison H (2011) Physical activity and hematologic cancer prevention. Recent Results Cancer Res 186:135–158PubMedCrossRef
34.
Institute of Medicine (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DC
35.
Polesel J, Talamini R, Montella M, Parpinel M, Dal Maso L, Crispo A, Crovatto M, Spina M, La Vecchia C, Franceschi S (2006) Linoleic acid, vitamin D and other nutrient intakes in the risk of non-Hodgkin lymphoma: an Italian case-control study. Ann Oncol 17(4):713–718PubMedCrossRef
36.
Lim U, Freedman DM, Hollis BW, Horst RL, Purdue MP, Chatterjee N, Weinstein SJ, Morton LM, Schatzkin A, Virtamo J, Linet MS, Hartge P, Albanes D (2009) A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Int J Cancer 124(4):979–986PubMedCrossRef
37.
Chang ET, Balter KM, Torrang A, Smedby KE, Melbye M, Sundstrom C, Glimelius B, Adami HO (2006) Nutrient intake and risk of non-Hodgkin’s lymphoma. Am J Epidemiol 164(12):1222–1232PubMedCrossRef
38.
Freedman DM, Looker AC, Chang SC, Graubard BI (2007) Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 99(21):1594–1602PubMedCrossRef
39.
Giovannucci E, Liu Y, Willett WC (2006) Cancer incidence and mortality and vitamin d in black and white male health professionals. Cancer Epidemiol Biomarkers Prev 15(12):2467–2472PubMedCrossRef
40.
Purdue MP, Freedman DM, Gapstur SM, Helzlsouer KJ, Laden F, Lim U, Maskarinec G, Rothman N, Shu XO, Stevens VL, Zeleniuch-Jacquotte A, Albanes D, Bertrand K, Weinstein SJ, Yu K, Irish L, Horst RL, Hoffman-Bolton J, Giovannucci EL, Kolonel LN, Snyder K, Willett W, Arslan AA, Hayes RB, Zheng W, Xiang YB, Hartge P (2010) Circulating 25-hydroxyvitamin D and risk of non-Hodgkin lymphoma: cohort consortium Vitamin D pooling project of rarer cancers. Am J Epidemiol 172(1):58–69PubMedCrossRef
41.
Millen AE, Bodnar LM (2008) Vitamin D assessment in population-based studies: a review of the issues. Am J Clin Nutr 87(4):1102S–1105SPubMed
42.
Holick MF (2008) Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 19(2):73–78PubMedCrossRef
43.
Halsall JA, Osborne JE, Potter L, Pringle JH, Hutchinson PE (2004) A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibility and prognosis in malignant melanoma. Br J Cancer 91(4):765–770PubMed
44.
Barroso E, Fernandez LP, Milne RL, Pita G, Sendagorta E, Floristan U, Feito M, Aviles JA, Martin-Gonzalez M, Arias JI, Zamora P, Blanco M, Lazaro P, Benitez J, Ribas G (2008) Genetic analysis of the vitamin D receptor gene in two epithelial cancers: melanoma and breast cancer case-control studies. BMC Cancer 8:385PubMedCrossRef
45.
Kizildag S, Ates H (2009) Treatment of K562 cells with 1,25-dihydroxyvitamin D(3) induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCL(XL), and p21. Ann Hematol
46.
Bai M, Vlachonikolis J, Agnantis NJ, Tsanou E, Dimou S, Nicolaides C, Stefanaki S, Pavlidis N, Kanavaros P (2001) Low expression of p27 protein combined with altered p53 and Rb/p16 expression status is associated with increased expression of cyclin A and cyclin B1 in diffuse large B-cell lymphomas. Mod Pathol 14(11):1105–1113PubMedCrossRef
47.
Cianferotti L, Cox M, Skorija K, Demay MB (2007) Vitamin D receptor is essential for normal keratinocyte stem cell function. Proc Natl Acad Sci USA 104(22):9428–9433PubMedCrossRef
48.
Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Broking E, Fehrenbach H, Wingen AM, Guran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365(5):410–421PubMedCrossRef
49.
Morton LM, Wang SS, Cozen W, Linet MS, Chatterjee N, Davis S, Severson RK, Colt JS, Vasef MA, Rothman N, Blair A, Bernstein L, Cross AJ, De Roos AJ, Engels EA, Hein DW, Hill DA, Kelemen LE, Lim U, Lynch CF, Schenk M, Wacholder S, Ward MH, Zahm SH, Chanock SJ, Cerhan JR, Hartge P (2008) Etiologic heterogeneity among non-Hodgkin lymphoma subtypes. Blood 112(13):5150–5160PubMedCrossRef
Metadata
Title
Early life sun exposure, vitamin D-related gene variants, and risk of non-Hodgkin lymphoma
Authors
Jennifer L. Kelly
Matthew T. Drake
Zachary S. Fredericksen
Yan W. Asmann
Mark Liebow
Tait D. Shanafelt
Andrew L. Feldman
Stephen M. Ansell
William R. Macon
Megan M. Herr
Alice H. Wang
Grzegorz S. Nowakowski
Timothy G. Call
Thomas M. Habermann
Susan L. Slager
Thomas E. Witzig
James R. Cerhan
Publication date
01-07-2012
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 7/2012
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-012-9967-0

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