Abstract
Low serum 25-hydroxyvitamin D (25OHD) concentrations have been associated with increased cancer risk, but the relative importance of seasonality, i.e. high summer concentrations versus low winter concentrations, is unclear. We investigated this issue in a high risk group: kidney transplant recipients with known increased risk of cancer and low vitamin D statuses. We examined the relationship between registered concentrations of 25OHD binned by quarter and subsequent risk of internal malignancy or cutaneous squamous cell carcinoma in 1112 kidney transplant recipients. Hazard ratios for internal malignancies were significantly increased with lower pre-diagnostic 25OHD concentrations in the first quarter of the year (January-March); a 1.4 fold increase (95%CI 1.1;1.7) per 10 nmol L−1 decrease in 25OHD. Except for women in April-June (1.3 (1.01;1.7) per 10 nmol L−1 decrease) pre-diagnostic 25OHD concentrations in the other quarters were not statistically significantly associated with internal malignancies. Higher 25OHD concentrations tended to be associated with the development of cutaneous squamous cell carcinomas, independent of the time of the year. Our study indicates that low wintertime 25OHD concentrations are associated with an increased risk of internal malignancies and that transplant recipients may benefit from wintertime vitamin D supplementation. Our findings need further corroboration, but suggest that the lowest concentrations of vitamin D, which occur in winter, are important for the risk of internal malignancies.
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S. Euvrard, J. Kanitakis and A. Claudy, Skin cancers after organ transplantation, N. Engl. J. Med., 2003, 348, 1681–1691.
H. C. Wisgerhof, L. G. van der Geest, J. W. de Fijter, G. W. Haasnoot, F. H. Claas, C. S. le Bouwes Bavinck, R. Willemze and J. N. Bouwes Bavinck, Incidence of cancer in kidney-transplant recipients: A long-term cohort study in a single center, Cancer Epidemiol., 2011, 35, 105–111.
C. A. Kulak, V. Z. Borba, J. Kulak Jr. and M. R. Custodio, Osteoporosis after transplantation, Curr. Osteoporos Rep., 2012, 10, 48–55.
S. Mazzaferro, M. Pasquali, F. Pugliese, F. Citterio, A. Gargiulo, S. Rotondi, L. Tartaglione, C. Conte, G. Pirro and F. Taggi, Distinct impact of vitamin D insufficiency on calcitriol levels in chronic renal failure and renal transplant patients: a role for FGF23, J. Nephrol., 2012, 25, 1108–1118.
H. Penny, S. Frame, F. Dickinson, G. Garrett, A. R. Young, R. Sarkany, N. Chitalia, G. Hampson and D. Goldsmith, Determinants of vitamin D status in long-term renal transplant patients, Clin. Transplant., 2012, 26, E617–E623.
K. Querings, M. Girndt, J. Geisel, T. Georg, W. Tilgen and J. Reichrath, 25-hydroxyvitamin D deficiency in renal transplant recipients, J. Clin. Endocrinol. Metab., 2006, 91, 526–529.
C. A. Keyzer, I. J. Riphagen, M. M. Joosten, G. Navis, A. C. Muller Kobold, I. P. Kema, S. J. Bakker, M. H. de Borst and N. Consortium, Associations of 25(OH) and 1,25(OH)2 vitamin D with long-term outcomes in stable renal transplant recipients, J. Clin. Endocrinol. Metab., 2015, 100, 81–89.
Health_Council_of_the_Netherlands, “Evaluatie van de voedingsnormen voor vitamine D”. Executive Summary in English Report Nr 2012/15 Publication no. 2012/15, The Hague, 2012.
M. F. Holick, Vitamin D: A millenium perspective, J. Cell. Biochem., 2003, 88, 296–307.
D. Bikle, Nonclassic actions of vitamin D, J. Clin. Endocrinol. Metab., 2009, 94, 26–34.
A. Verstuyf, G. Carmeliet, R. Bouillon and C. Mathieu, Vitamin D: a pleiotropic hormone, Kidney Int., 2010, 78, 140–145.
A. W. Norman, From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health, Am. J. Clin. Nutr., 2008, 88, 491S–499S.
T. C. Chen, G. G. Schwartz, K. L. Burnstein, B. L. Lokeshwar and M. F. Holick, The in vitro evaluation of 25-hydroxyvitamin D3 and 19-nor-1alpha,25-dihydroxyvi-tamin D2 as therapeutic agents for prostate cancer, Clin. Cancer Res., 2000, 6, 901–908.
K. Colston, M. J. Colston and D. Feldman, 1,25-dihydroxyvi-tamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture, Endocrinology, 1981, 108, 1083–1086.
H. Rebel, C. D. der Spek, D. Salvatori, J. P. van Leeuwen, E. C. Robanus-Maandag and F. R. de Gruijl, UV exposure inhibits intestinal tumor growth and progression to malignancy in intestine-specific Apc mutant mice kept on low vitamin D diet, Int. J. Cancer, 2015, 136, 271–277.
K. Wu, D. Feskanich, C. S. Fuchs, W. C. Willett, B. W. Hollis and E. L. Giovannucci, A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer, J. Natl. Cancer Inst., 2007, 99, 1120–1129.
M. Jenab, H. B. Bueno-de-Mesquita, P. Ferrari, F. J. van Duijnhoven, T. Norat, T. Pischon, E. H. Jansen, N. Slimani, G. Byrnes, S. Rinaldi, A. Tjonneland, A. Olsen, K. Overvad, M. C. Boutron-Ruault, F. Clavel-Chapelon, S. Morois, R. Kaaks, J. Linseisen, H. Boeing, M. M. Bergmann, A. Trichopoulou, G. Misirli, D. Trichopoulos, F. Berrino, P. Vineis, S. Panico, D. Palli, R. Tumino, M. M. Ros, C. H. van Gils, P. H. Peeters, M. Brustad, E. Lund, M. J. Tormo, E. Ardanaz, L. Rodriguez, M. J. Sanchez, M. Dorronsoro, C. A. Gonzalez, G. Hallmans, R. Palmqvist, A. Roddam, T. J. Key, K. T. Khaw, P. Autier, P. Hainaut and E. Riboli, Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study, Br. Med. J., 2010, 340, b5500.
A. M. Mondul, S. J. Weinstein, T. M. Layne and D. Albanes, Vitamin D and Cancer Risk and Mortality: State of the Science, Gaps, and Challenges, Epidemiol. Rev., 2017, 39, 28–48.
D. Ducloux, C. Courivaud, J. Bamoulid, A. Kazory, G. Dumoulin and J. M. Chalopin, Pretransplant serum vitamin D levels and risk of cancer after renal transplantation, Transplantation, 2008, 85, 1755–1759.
U. Lim, D. M. Freedman, B. W. Hollis, R. L. Horst, M. P. Purdue, N. Chatterjee, S. J. Weinstein, L. M. Morton, A. Schatzkin, J. Virtamo, M. S. Linet, P. Hartge and D. Albanes, A prospective investigation of serum 25-hydro-xyvitamin D and risk of lymphoid cancers, Int. J. Cancer, 2009, 124, 979–986.
R. Takahashi, T. Mizoue, T. Otake, J. Fukumoto, O. Tajima, S. Tabata, H. Abe, K. Ohnaka and S. Kono, Circulating vitamin D and colorectal adenomas in Japanese men, Cancer Sci., 2010, 101, 1695–1700.
H. M. Macdonald, A. Mavroeidi, R. J. Barr, A. J. Black, W. D. Fraser and D. M. Reid, Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D, Bone, 2008, 42, 996–1003.
H. E. Hanwell, R. Vieth, D. E. Cole, A. Scillitani, S. Modoni, V. Frusciante, G. Ritrovato, I. Chiodini, S. Minisola and V. Carnevale, Sun exposure questionnaire predicts circulating 25-hydroxyvitamin D concentrations in Caucasian hospital workers in southern Italy, J. Steroid Biochem. Mol. Biol., 2010, 121, 334–337.
K. Nakamura, M. Nashimoto and M. Yamamoto, Summer/ winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women, Int. J. Biometeorol., 2000, 44, 186–189.
E. Thieden, P. A. Philipsen, J. Heydenreich and H. C. Wulf, Vitamin D level in summer and winter related to measured UVR exposure and behavior, Photochem. Photobiol., 2009, 85, 1480–1484.
A. R. Webb, R. Kift, M. T. Durkin, S. J. O’Brien, A. Vail, J. L. Berry and L. E. Rhodes, The role of sunlight exposure in determining the vitamin D status of the U.K. white adult population, Br.J. Dermatol., 2010, 163, 1050–1055.
S. J. Wimalawansa, Non-musculoskeletal benefits of vitamin D, J. Steroid Biochem. Mol. Biol., 2018, 175, 60–81.
B. Goulao, F. Stewart, J. A. Ford, G. MacLennan and A. Avenell, Cancer and vitamin D supplementation: a systematic review and meta-analysis, Am. J. Clin. Nutr., 2018, 107, 652–663.
G. Bjelakovic, L. L. Gluud, D. Nikolova, K. Whitfield, G. Krstic, J. Wetterslev and C. Gluud, Vitamin D supplementation for prevention of cancer in adults, Cochrane Database Syst. Rev., 2014, CD007469, DOI: 10.1002/ 14651858.CD007469.pub2.
L. Rejnmark, L. S. Bislev, K. D. Cashman, G. Eiriksdottir, M. Gaksch, M. Grubler, G. Grimnes, V. Gudnason, P. Lips, S. Pilz, N. M. van Schoor, M. Kiely and R. Jorde, Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data, PLoS One, 2017, 12, e0180512.
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This work was supported by a grant of the Foundation for General Light Therapy (the Dutch legacy trust “Stichting voor Algemeene Lichttherapie) without any involvement in the study.
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de Gruijl, F.R., Wolterbeek, R., Pavel, S. et al. Low wintertime pre-diagnostic vitamin D status is associated with an increased risk of internal malignancies in kidney transplant recipients. Photochem Photobiol Sci 17, 1946–1955 (2018). https://doi.org/10.1039/c7pp00404d
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DOI: https://doi.org/10.1039/c7pp00404d