Cancer Causes & Control

, 22:1731 | Cite as

Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses’ Health Study

  • Kimberly A. Bertrand
  • Ellen T. Chang
  • Gregory A. Abel
  • Shumin M. Zhang
  • Donna Spiegelman
  • Abrar A. Qureshi
  • Francine Laden
Original Paper



Case–control studies suggest increased sun exposure reduces non-Hodgkin lymphoma (NHL) risk. Evidence from prospective cohort studies, however, is limited and inconsistent. We evaluated the association between ambient ultraviolet radiation (UV) exposure and NHL in a nationwide cohort of women, the Nurses’ Health Study (NHS).


Between 1976 and 2006, we identified 1064 incident NHL cases among 115,482 women in the prospective NHS. Exposures assessed included average annual UV-B flux based on residence at various times during life, vitamin D intake, and predicted plasma 25-hydroxyvitamin D levels. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of all NHL and histologic subtypes using Cox proportional hazards models.


NHL risk was increased for women residing in areas of high ambient UV radiation (UV-B flux >113 R–B count × 10−4) compared to those with lower exposure (<113), with positive linear trends at all time points. The multivariable-adjusted RR for high UV area at age 15 was 1.21 (95% CI: 1.00, 1.47; p-trend < 0.01). There was no evidence of statistical heterogeneity by subtype, although power was limited for subtype analyses. We observed no association between vitamin D measures and risk of NHL overall or by subtype.


Our findings do not support the hypothesis of a protective effect of UV radiation exposure on NHL risk. We found no association between vitamin D and NHL risk.


Non-Hodgkin lymphoma Sunlight Ultraviolet radiation Vitamin D Epidemiology 



This work was supported by the National Institutes of Health (CA87969 and CA098122). K.A.B. was supported by the Training Program in Environmental Health Sciences (T32 ES007155) and the Nutritional Epidemiology of Cancer Education and Career Development Program (R25 CA098566).

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    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):865–871. doi: 10.1002/ijc.20470 PubMedCrossRefGoogle Scholar
  2. 2.
    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):199–209. doi: 10.1093/jnci/dji022 PubMedCrossRefGoogle Scholar
  3. 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):1045–1052. doi: 10.1007/s10552-006-0040-8 PubMedCrossRefGoogle Scholar
  4. 4.
    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):2445–2451. doi: 10.1002/ijc.22492 PubMedCrossRefGoogle Scholar
  5. 5.
    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):2388–2395. doi: 10.1016/j.ejca.2007.06.018 PubMedCrossRefGoogle Scholar
  6. 6.
    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):144–154. doi: 10.1002/ijc.23003 PubMedCrossRefGoogle Scholar
  7. 7.
    Boffetta P, van der Hel O, Kricker A, Nieters A, de Sanjose S, Maynadie M, Cocco PL, Staines A, Becker N, Font R, Mannetje A, Goumas C, Brennan P (2008) Exposure to ultraviolet radiation and risk of malignant lymphoma and multiple myeloma—a multicentre European case-control study. Int J Epidemiol 37(5):1080–1094. doi: 10.1093/ije/dyn092 PubMedCrossRefGoogle Scholar
  8. 8.
    Kelly JL, Friedberg JW, Calvi LM, van Wijngaarden E, Fisher SG (2010) A case-control study of ultraviolet radiation exposure, vitamin D, and lymphoma risk in adults. Cancer Causes Control 21(8):1265–1275. doi: 10.1007/s10552-010-9554-1 PubMedCrossRefGoogle Scholar
  9. 9.
    Egan KM, Sosman JA, Blot WJ (2005) Sunlight and reduced risk of cancer: is the real story vitamin D? J Natl Cancer Inst 97(3):161–163. doi: 10.1093/jnci/dji047 PubMedCrossRefGoogle Scholar
  10. 10.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281PubMedCrossRefGoogle Scholar
  11. 11.
    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):668–672PubMedCrossRefGoogle Scholar
  12. 12.
    Chen S, Sims GP, Chen XX, Gu YY, Lipsky PE (2007) Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179(3):1634–1647. doi: 179/3/1634 PubMedGoogle Scholar
  13. 13.
    Kelly JL, Friedberg JW, Calvi LM, van Wijngaarden E, Fisher SG (2009) Vitamin D and non-Hodgkin lymphoma risk in adults: a review. Cancer Invest 27(9):942–951. doi: 10.3109/07357900902849632 PubMedCrossRefGoogle Scholar
  14. 14.
    Negri E (2010) Sun exposure, vitamin D, and risk of Hodgkin and non-Hodgkin lymphoma. Nutr Cancer 62(7):878–882. doi: 10.1080/01635581.2010.509535 PubMedCrossRefGoogle Scholar
  15. 15.
    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 172:58–69. doi: 10.1093/aje/kwq117 PubMedCrossRefGoogle Scholar
  16. 16.
    Veierød 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):1569–1576. doi: 10.1158/1055-9965.EPI-10-0115 PubMedCrossRefGoogle Scholar
  17. 17.
    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. doi: 10.1182/blood-2011-02-336065
  18. 18.
    Rich-Edwards JW, Corsano KA, Stampfer MJ (1994) Test of the national death index and equifax nationwide death search. Am J Epidemiol 140:1016–1019PubMedGoogle Scholar
  19. 19.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer (IARC) Press, Lyon, FranceGoogle Scholar
  20. 20.
    Scotto J, Fears TR, Fraumeni JF Jr (1996) Solar radiation. In: Schottenfeld D, Fraumeni JF Jr (eds) Cancer epidemiology and prevention, 2nd edn. Oxford University Press, New York, pp 355–372Google Scholar
  21. 21.
    Scotto J, Cotton G, Urbach F, Berger D, Fears T (1988) Biologically effective ultraviolet radiation: surface measurements in the United States, 1974 to 1985. Science 239(4841 Pt 1):762–764Google Scholar
  22. 22.
    Fears TR, Bird CC, Guerry Dt, Sagebiel RW, Gail MH, Elder DE, Halpern A, Holly EA, Hartge P, Tucker MA (2002) Average midrange ultraviolet radiation flux and time outdoors predict melanoma risk. Cancer Res 62(14):3992–3996PubMedGoogle Scholar
  23. 23.
    Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, Hennekens CH, Speizer FE (1985) Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122(1):51–65PubMedGoogle Scholar
  24. 24.
    Willett WC, Sampson L, Browne ML, Stampfer MJ, Rosner B, Hennekens CH, Speizer FE (1988) The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol 127(1):188–199PubMedGoogle Scholar
  25. 25.
    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–1688S. doi: 80/6/1678S PubMedGoogle Scholar
  26. 26.
    Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC (2006) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98(7):451–459. doi: 10.1093/jnci/djj101 PubMedCrossRefGoogle Scholar
  27. 27.
    Durrleman S, Simon R (1989) Flexible regression models with cubic splines. Stat Med 8(5):551–561PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang S, Hunter DJ, Rosner BA, Colditz GA, Fuchs CS, Speizer FE, Willett WC (1999) Dietary fat and protein in relation to risk of non-Hodgkin’s lymphoma among women. J Natl Cancer Inst 91(20):1751–1758PubMedCrossRefGoogle Scholar
  29. 29.
    Morton LM, Hartge P, Holford TR, Holly EA, Chiu BC, Vineis P, Stagnaro E, Willett EV, Franceschi S, La Vecchia C, Hughes AM, Cozen W, Davis S, Severson RK, Bernstein L, Mayne ST, Dee FR, Cerhan JR, Zheng T (2005) Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph). Cancer Epidemiol Biomarkers Prev 14(4):925–933. doi: 10.1158/1055-9965.EPI-04-0693 PubMedCrossRefGoogle Scholar
  30. 30.
    Larsson SC, Wolk A (2007) Obesity and risk of non-Hodgkin’s lymphoma: a meta-analysis. Int J Cancer 121(7):1564–1570. doi: 10.1002/ijc.22762 PubMedCrossRefGoogle Scholar
  31. 31.
    Greenland S (1989) Modeling and variable selection in epidemiologic analysis. Am J Public Health 79(3):340–349PubMedCrossRefGoogle Scholar
  32. 32.
    Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65 (4 Suppl):1220S–1228S; discussion 1229S–1231SGoogle Scholar
  33. 33.
    Anderson TW (1984) Introduction to multivariate statistics, 2nd edn. Wiley, New YorkGoogle Scholar
  34. 34.
    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):1255–1264. doi: 10.1093/aje/kwm020 PubMedCrossRefGoogle Scholar
  35. 35.
    Adami J, Gridley G, Nyren O, Dosemeci M, Linet M, Glimelius B, Ekbom A, Zahm SH (1999) Sunlight and non-Hodgkin’s lymphoma: a population-based cohort study in Sweden. Int J Cancer 80(5):641–645. doi: 10.1002/(SICI)1097-0215(19990301)80 PubMedCrossRefGoogle Scholar
  36. 36.
    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):321–325. doi: 10.1016/j.jphotobiol.2010.08.001 PubMedCrossRefGoogle Scholar
  37. 37.
    Grandin L, Orsi L, Troussard X, Monnereau A, Berthou C, Fenaux P, Marit G, Soubeyran P, Huguet F, Milpied N, Leporrier M, Hemon D, Clavel J (2008) UV radiation exposure, skin type and lymphoid malignancies: results of a French case-control study. Cancer Causes Control 19(3):305–315. doi: 10.1007/s10552-007-9093-6 PubMedCrossRefGoogle Scholar
  38. 38.
    Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC (2007) Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol 103(3–5):708–711. doi: 10.1016/j.jsbmb.2006.12.007 PubMedCrossRefGoogle Scholar
  39. 39.
    Giovannucci E (2005) The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control 16(2):83–95. doi: 10.1007/s10552-004-1661-4 PubMedCrossRefGoogle Scholar
  40. 40.
    Li H, Stampfer MJ, Hollis JB, Mucci LA, Gaziano JM, Hunter D, Giovannucci EL, Ma J (2007) A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med 4(3):e103. doi: 10.1371/journal.pmed.0040103
  41. 41.
    Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL (2007) A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst 99(14):1120–1129. doi: 10.1093/jnci/djm038 PubMedCrossRefGoogle Scholar
  42. 42.
    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):1222–1232. doi: 10.1093/aje/kwj330 PubMedCrossRefGoogle Scholar
  43. 43.
    Erber E, Maskarinec G, Lim U, Kolonel LN (2010) Dietary vitamin D and risk of non-Hodgkin lymphoma: the multiethnic cohort. Br J Nutr 103(4):581–584. doi: 10.1017/S0007114509992029 PubMedCrossRefGoogle Scholar
  44. 44.
    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):1594–1602. doi: 10.1093/jnci/djm204 PubMedCrossRefGoogle Scholar
  45. 45.
    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):979–986. doi: 10.1002/ijc.23984 PubMedCrossRefGoogle Scholar
  46. 46.
    Di Nuzzo S, Sylva-Steenland RM, Koomen CW, Nakagawa S, van Breemen M, de Rie MA, Das PK, Bos JD, Teunissen MB (2002) UVB irradiation of normal human skin favors the development of type-2 T-cells in vivo and in primary dermal cell cultures. Photochem Photobiol 76(3):301–309PubMedCrossRefGoogle Scholar
  47. 47.
    Norval M (2001) Effects of solar radiation on the human immune system. J Photochem Photobiol B 63(1–3):28–40. doi: S1011134401002007 PubMedCrossRefGoogle Scholar
  48. 48.
    Adami J, Frisch M, Yuen J, Glimelius B, Melbye M (1995) Evidence of an association between non-Hodgkin’s lymphoma and skin cancer. BMJ 310(6993):1491–1495PubMedCrossRefGoogle Scholar
  49. 49.
    Goggins WB, Finkelstein DM, Tsao H (2001) Evidence for an association between cutaneous melanoma and non-Hodgkin lymphoma. Cancer 91(4):874–880. doi: 10.1002/1097-0142(20010215)91:4<874 PubMedCrossRefGoogle Scholar
  50. 50.
    Hughes AM, Armstrong BK, Vajdic CM, Turner J, Grulich A, Fritschi L, Milliken S, Kaldor J, Benke G, Kricker A (2004) Pigmentary characteristics, sun sensitivity and non-Hodgkin lymphoma. Int J Cancer 110(3):429–434. doi: 10.1002/ijc.20128 PubMedCrossRefGoogle Scholar
  51. 51.
    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, Hoar Zahm S, Chanock SJ, Cerhan JR, Hartge P (2008) Etiologic heterogeneity among non-Hodgkin lymphoma subtypes. Blood 112(13):5150–5160. doi: 10.1182/blood-2008-01-133587 PubMedCrossRefGoogle Scholar
  52. 52.
    Abel GA, Bertrand KA, Earle CC, Laden F (2010) Outcomes for lymphoid malignancies in the Nurses’ Health Study (NHS) as compared to the Surveillance, Epidemiology and End Results (SEER) Program. Hematol Oncol 28(3):133–136. doi: 10.1002/hon.930 PubMedGoogle Scholar
  53. 53.
    Robinson JK, Rigel DS, Amonette RA (1997) Trends in sun exposure knowledge, attitudes, and behaviors: 1986 to 1996. J Am Acad Dermatol 37(2 Pt 1):179–186. doi: 10.1016/S0190-9622(97)80122-3 Google Scholar
  54. 54.
    Brown DL, Feskanich D, Sanchez BN, Rexrode KM, Schernhammer ES, Lisabeth LD (2009) Rotating night shift work and the risk of ischemic stroke. Am J Epidemiol 169(11):1370–1377. doi: 10.1093/aje/kwp056 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Kimberly A. Bertrand
    • 1
    • 2
  • Ellen T. Chang
    • 3
    • 4
  • Gregory A. Abel
    • 5
  • Shumin M. Zhang
    • 6
  • Donna Spiegelman
    • 1
    • 7
  • Abrar A. Qureshi
    • 2
    • 8
  • Francine Laden
    • 1
    • 2
    • 9
  1. 1.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  2. 2.Channing Laboratory, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Cancer Prevention Institute of CaliforniaFremontUSA
  4. 4.Division of Epidemiology, Department of Health Research and PolicyStanford University School of MedicineStanfordUSA
  5. 5.Center for Outcomes and Policy Research, Department of Medical Oncology, Dana-Farber Cancer InstituteHarvard Medical SchoolBostonUSA
  6. 6.Division of Preventive Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  7. 7.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  8. 8.Clinical Research Program, Department of DermatologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  9. 9.Department of Environmental HealthHarvard School of Public HealthBostonUSA

Personalised recommendations