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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Research

Association of serum 25-hydroxy-vitamin D concentration and risk of mortality in cancer survivors in the United States

Authors: Xiaofei Mo, Chen He, Fengfeng Han, Hui Yan, Xueqin Chen, Yuetao Wang, Mingge Zhou

Published in: BMC Cancer | Issue 1/2024

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Abstract

Purpose

Cancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors.

Methods

A prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose–response relationship between serum 25(OH)D concentrations and mortality.

Results

The study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56–0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32–0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45–0.99). RCS curves revealed “L-shaped” associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009).

Conclusion

Elevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.
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Literature
1.
Latic N, Erben RG. Vitamin D and cardiovascular disease, with emphasis on hypertension, atherosclerosis, and heart failure. Int J Mol Sci. 2020;21(18):6483.PubMedPubMedCentralCrossRef
2.
3.
Jeon SM, Shin EA. Exploring vitamin D metabolism and function in cancer. Exp Mol Med. 2018;50(4):1–14.PubMed
4.
Zhang Y, Fang F, Tang J, Jia L, Feng Y, Xu P, Faramand A. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ. 2019;366:l4673.PubMedPubMedCentralCrossRef
5.
6.
Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, Cicin I, Merle P, Chen Y, Park JW, Blanc JF, Bolondi L, Klümpen HJ, Chan SL, Zagonel V, Pressiani T, Ryu MH, Venook AP, Hessel C, Borgman-Hagey AE, Schwab G, Kelley RK. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.PubMedPubMedCentralCrossRef
7.
Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O’Neil P, Park J, Peters A, Phillips LS, Pratley R, Raskin P, Rasouli N, Robbins D, Rosen C, Vickery EM, Staten M. Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med. 2019;381(6):520–30.PubMedPubMedCentralCrossRef
8.
9.
10.
Chang SW, Lee HC. Vitamin D and health - the missing vitamin in humans. Pediatr Neonatol. 2019;60(3):237–44.PubMedCrossRef
11.
Zhao G, Ford ES, Li C, Croft JB. Serum 25-hydroxyvitamin D levels and all-cause and cardiovascular disease mortality among US adults with hypertension: the NHANES linked mortality study. J Hypertens. 2012;30(2):284–9.PubMedCrossRef
12.
Wan Z, Guo J, Pan A, Chen C, Liu L, Liu G. Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with diabetes. Diabetes Care. 2021;44(2):350–7.PubMedCrossRef
13.
Chen X, Zhou M, Yan H, Chen J, Wang Y, Mo X. Association of serum total 25-hydroxy-vitamin D concentration and risk of all-cause, cardiovascular and malignancies-specific mortality in patients with hyperlipidemia in the United States. Front Nutr. 2022;9:971720.PubMedPubMedCentralCrossRef
14.
Kuznia S, Zhu A, Akutsu T, Buring JE, Camargo CA Jr, Cook NR, Chen LJ, Cheng TD, Hantunen S, Lee IM, Manson JE, Neale RE, Scragg R, Shadyab AH, Sha S, Sluyter J, Tuomainen TP, Urashima M, Virtanen JK, Voutilainen A, Wactawski-Wende J, Waterhouse M, Brenner H, Schöttker B. Efficacy of vitamin D(3) supplementation on cancer mortality: Systematic review and individual patient data meta-analysis of randomised controlled trials. Ageing Res Rev. 2023;87:101923.PubMedPubMedCentralCrossRef
15.
Gnagnarella P, Muzio V, Caini S, Raimondi S, Martinoli C, Chiocca S, Miccolo C, Bossi P, Cortinovis D, Chiaradonna F, Palorini R, Facciotti F, Bellerba F, Canova S, Gandini S. Vitamin D supplementation and cancer mortality: narrative review of observational studies and clinical trials. Nutrients. 2021;13(9):3285.PubMedPubMedCentralCrossRef
16.
Giustina A, Adler RA, Binkley N, Bollerslev J, Bouillon R, Dawson-Hughes B, Ebeling PR, Feldman D, Formenti AM, Lazaretti-Castro M, Marcocci C, Rizzoli R, Sempos CT, Bilezikian JP. Consensus statement from 2(nd) international conference on controversies in vitamin D. Rev Endocr Metab Disor. 2020;21(1):89–116.CrossRef
17.
Ahluwalia N, Dwyer J, Terry A, Moshfegh A, Johnson C. Update on NHANES dietary data: focus on collection, release, analytical considerations, and uses to inform public policy. Adv Nutr. 2016;7(1):121–34.PubMedPubMedCentralCrossRef
18.
Saenger AK, Laha TJ, Bremner DE, Sadrzadeh SM. Quantification of serum 25-hydroxyvitamin D(2) and D(3) using HPLC-tandem mass spectrometry and examination of reference intervals for diagnosis of vitamin D deficiency. Am J Clin Pathol. 2006;125(6):914–20.PubMedCrossRef
19.
Weir CB, Jan A. BMI Classification Percentile And Cut Off Points. In: StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2023. PMID: 31082114
20.
Rattan P, Penrice DD, Ahn JC, Ferrer A, Patnaik M, Shah VH, Kamath PS, Mangaonkar AA, Simonetto DA. Inverse association of telomere length with liver disease and mortality in the US population. Hepatol Commun. 2022;6(2):399–410.PubMedCrossRef
21.
Krebs-Smith SM, Pannucci TE, Subar AF, Kirkpatrick SI, Lerman JL, Tooze JA, Wilson MM, Reedy J. Update of the healthy eating index: HEI-2015. J Acad Nutr Diet. 2018;118(9):1591–602.PubMedPubMedCentralCrossRef
22.
Chen L, Cai M, Li H, Wang X, Tian F, Wu Y, Zhang Z, Lin H. Risk/benefit tradeoff of habitual physical activity and air pollution on chronic pulmonary obstructive disease: findings from a large prospective cohort study. BMC Med. 2022;20(1):70.PubMedPubMedCentralCrossRef
23.
Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, Carty C, Chaput JP, Chastin S, Chou R, Dempsey PC, DiPietro L, Ekelund U, Firth J, Friedenreich CM, Garcia L, Gichu M, Jago R, Katzmarzyk PT, Lambert E, Leitzmann M, Milton K, Ortega FB, Ranasinghe C, Stamatakis E, Tiedemann A, Troiano RP, van der Ploeg HP, Wari V, Willumsen JF. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54(24):1451–62.PubMedCrossRef
24.
Charlson ME, Carrozzino D, Guidi J, Patierno C. Charlson comorbidity index: a critical review of clinimetric properties. Psychother Psychosom. 2022;91(1):8–35.PubMedCrossRef
25.
Chen TC, Clark J, Riddles MK, Mohadjer LK, Fakhouri THI. National health and nutrition examination survey, 2015–2018: sample design and estimation procedures. Vital Health Stat 2. 2020;184:1–35.
26.
Gallagher JC, Rosen CJ. Vitamin D: 100 years of discoveries, yet controversy continues. Lancet Diabetes Endocrinol. 2023;11(5):362–74.PubMedCrossRef
27.
28.
Kim H, Yuan C, Nguyen LH, Ng K, Giovannucci EL. Prediagnostic vitamin D status and colorectal cancer survival by vitamin D binding protein isoforms in US cohorts. J Clin Endocrinol Metab. 2023;108(6):e223–9.PubMedCrossRef
29.
Mondul AM, Weinstein SJ, Moy KA, Männistö S, Albanes D. Circulating 25-hydroxyvitamin D and prostate cancer survival. Cancer Epidemiol Biomarkers Prev. 2016;25(4):665–9.PubMedPubMedCentralCrossRef
30.
Weinstein SJ, Mondul AM, Layne TM, Yu K, Huang J, Stolzenberg-Solomon RZ, Ziegler RG, Purdue MP, Huang WY, Abnet CC, Freedman ND, Albanes D. Prediagnostic serum vitamin D, vitamin D binding protein isoforms, and cancer survival. JNCI Cancer Spectr. 2022;6(2):pkac019.PubMedPubMedCentralCrossRef
31.
Cohen JB, Brown NJ, Brown SA, Dent S, van Dorst DCH, Herrmann SM, Lang NN, Oudit GY, Touyz RM. Cancer therapy-related hypertension: a scientific statement from the American heart association. Hypertension. 2023;80(3):e46–57.PubMedCrossRef
32.
Gebauer J, Higham C, Langer T, Denzer C, Brabant G. Long-term endocrine and metabolic consequences of cancer treatment: a systematic review. Endocr Rev. 2019;40(3):711–67.PubMedCrossRef
33.
Guilcher GMT, Rivard L, Huang JT, Wright NAM, Anderson L, Eissa H, Pelletier W, Ramachandran S, Schechter T, Shah AJ, Wong K, Chow EJ. Immune function in childhood cancer survivors: a children’s oncology group review. Lancet Child Adolesc Health. 2021;5(4):284–94.PubMedPubMedCentralCrossRef
34.
Larsen EH, Mellblom AV, Larsen MH, Ruud E, Thorsen L, Petersen NN, Larsen HB, Fridh MK, Lie HC. Perceived barriers and facilitators to physical activity in childhood cancer survivors and their parents: a large-scale interview study from the International PACCS Study. Pediatr Blood Cancer. 2023;70(1):e30056.PubMedCrossRef
35.
Lovelace DL, McDaniel LR, Golden D. Long-term effects of breast cancer surgery, treatment, and survivor care. J Midwifery Womens Health. 2019;64(6):713–24.PubMedCrossRef
36.
Todd BL, Moskowitz MC, Ottati A, Feuerstein M. Stressors, stress response, and cancer recurrence: a systematic review. Cancer Nurs. 2014;37(2):114–25.PubMedCrossRef
37.
Mo X, Zhou M, Yan H, Chen X, Wang Y. Estimating the risk of developing secondary hematologic malignancies in patients with T1/T2 prostate cancer undergoing diverse treatment modalities: a large population-based study. Cancer Med. 2021;10(15):5338–46.PubMedPubMedCentralCrossRef
38.
Ko KY, Kao CH, Lin CL, Huang WS, Yen RF. (131)I treatment for thyroid cancer and the risk of developing salivary and lacrimal gland dysfunction and a second primary malignancy: a nationwide population-based cohort study. Eur J Nucl Med Mol Imaging. 2015;42(8):1172–8.PubMedCrossRef
39.
Jang YC, Huang HL, Leung CY. Association of hormone replacement therapy with mortality in colorectal cancer survivor: a systematic review and meta-analysis. BMC Cancer. 2019;19(1):1199.PubMedPubMedCentralCrossRef
40.
Zhang JJ, Yu HC, Li Y, Zhang YB, Geng TT, Lu Q, Liao YF, Guo KQ, Du L, Ruan HL, Yang K, Liu G, Pan A. Association between serum 25-hydroxy vitamin D concentrations and mortality among individuals with metabolic dysfunction-associated fatty liver disease: a prospective cohort study. Am J Clin Nutr. 2022;116(5):1409–17.PubMedCrossRef
41.
Zhang P, Guo D, Xu B, Huang C, Yang S, Wang W, Liu W, Deng Y, Li K, Liu D, Lin J, Wei X, Huang Y, Zhang H. Association of serum 25-hydroxyvitamin D with cardiovascular outcomes and all-cause mortality in individuals with prediabetes and diabetes: results from the UK biobank prospective cohort study. Diabetes Care. 2022;45(5):1219–29.PubMedCrossRef
42.
Kato I, Sun J, Hastert TA, Abrams J, Larson JC, Bao W, Shadyab AH, Mouton C, Qi L, Warsinger ML, Manson JE. Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: Extended follow-up of the Women’s Health Initiative calcium-vitamin D trial. Int J Cancer. 2023;153(5):1035–42.PubMedCrossRef
43.
Fu H, Tang Z, Wang Y, Ding X, Rinaldi G, Rahmani J, Xing F. Relationship between vitamin D level and mortality in adults with psoriasis: a retrospective cohort study of NHANES data. Clin Ther. 2021;43(2):e33–8.PubMedCrossRef
44.
Xiao Q, Cai B, Yin A, Huo H, Lan K, Zhou G, Shen L, He B. L-shaped association of serum 25-hydroxyvitamin D concentrations with cardiovascular and all-cause mortality in individuals with osteoarthritis: results from the NHANES database prospective cohort study. BMC Med. 2022;20(1):308.PubMedPubMedCentralCrossRef
45.
Geng T, Lu Q, Wan Z, Guo J, Liu L, Pan A, Liu G. Association of serum 25-hydroxyvitamin D concentrations with risk of dementia among individuals with type 2 diabetes: a cohort study in the UK Biobank. PLoS Med. 2022;19(1):e1003906.PubMedPubMedCentralCrossRef
46.
Wan Z, Geng T, Li R, Chen X, Lu Q, Lin X, Chen L, Guo Y, Liu L, Shan Z, Pan A, Manson JE, Liu G. Vitamin D status, genetic factors, and risks of cardiovascular disease among individuals with type 2 diabetes: a prospective study. Am J Clin Nutr. 2022;116(5):1389–99.PubMedCrossRef
47.
Li Y, Hu P, Wu X, Zou Q, Liu X, Liu J, Fu Y. Association between serum vitamin D and refractive status in United States adolescents: A cross-sectional study. Front Nutr. 2022;9:1038963.PubMedPubMedCentralCrossRef
48.
Lin X, Chen X, Liu S, Deng Y, Wang Y, Lu Q, Li R, Ou Y, Tian Q, Liao Y, Cui G, Yang K, Pan A, Liu G. Associations of Serum 25(OH)D with risk of recurrent cardiovascular events in individuals with coronary heart disease. J Clin Endocrinol Metab. 2023;108(12):e1712–9.PubMedCrossRef
49.
Zhu K, Knuiman M, Divitini M, Hung J, Lim EM, Cooke BR, Walsh JP. Serum 25-hydroxyvitamin D as a predictor of mortality and cardiovascular events: a 20-year study of a community-based cohort. Clin Endocrinol (Oxf). 2018;88(1):154–63.PubMedCrossRef
50.
Sohl E, de Jongh RT, Heymans MW, van Schoor NM, Lips P. Thresholds for serum 25(OH)D concentrations with respect to different outcomes. J Clin Endocrinol Metab. 2015;100(6):2480–8.PubMedCrossRef
51.
Ye K, Tang F, Liao X, Shaw BA, Deng M, Huang G, Qin Z, Peng X, Xiao H, Chen C, Liu X, Ning L, Wang B, Tang N, Li M, Xu F, Lin S, Yang J. Does serum vitamin D level affect COVID-19 infection and its severity?-A case-control study. J Am Coll Nutr. 2021;40(8):724–31.PubMedCrossRef
52.
53.
Li Q, Li Y, Jiang H, Xiao Z, Wu X, Zhang H, Zhao Y, Du F, Chen Y, Wu Z, Li J, Hu W, Cho CH, Shen J, Li M. Vitamin D suppressed gastric cancer cell growth through downregulating CD44 expression in vitro and in vivo. Nutrition. 2021;91–92:111413.PubMedCrossRef
54.
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365–408.PubMedCrossRef
55.
Höbaus J, Thiem U, Hummel DM, Kallay E. Role of calcium, vitamin D, and the extrarenal vitamin D hydroxylases in carcinogenesis. Anticancer Agents Med Chem. 2013;13(1):20–35.PubMedPubMedCentralCrossRef
56.
Duffy MJ, Murray A, Synnott NC, O’Donovan N, Crown J. Vitamin D analogues: Potential use in cancer treatment. Crit Rev Oncol Hematol. 2017;112:190–7.PubMedCrossRef
57.
Pirrotta F, Cavati G, Mingiano C, Merlotti D, Nuti R, Gennari L, Palazzuoli A. Vitamin D deficiency and cardiovascular mortality: retrospective analysis “Siena osteoporosis” cohort. Nutrients. 2023;15(15):3303.PubMedPubMedCentralCrossRef
58.
Kim S, Cho J, Shin DW, Jeong SM, Kang D. Racial differences in long-term social, physical, and psychological health among adolescent and young adult cancer survivors. BMC Medicine. 2023;21(1):289.PubMedPubMedCentralCrossRef
59.
Zhang Y, Wu Y, Zhang Y, Cao D, He H, Cao X, Wang Y, Jia Z, Jiang J. Dietary inflammatory index, and depression and mortality risk associations in U.S. adults, with a special focus on cancer survivors. Front Nutr. 2022;9:1034323.PubMedPubMedCentralCrossRef
60.
Yngve A, Haapala I, Hodge A, McNeill G, Tseng M. Vitamin D, dietary patterns, and food acquisition. Public Health Nutr. 2011;14(9):1511–2.PubMedCrossRef
61.
Brouwer-Brolsma EM, Vaes AMM, van der Zwaluw NL, van Wijngaarden JP, Swart KMA, Ham AC, van Dijk SC, Enneman AW, Sohl E, van Schoor NM, van der Velde N, Uitterlinden AG, Lips P, Feskens EJM, Dhonukshe-Rutten RAM, de Groot LCPGM. Relative importance of summer sun exposure, vitamin D intake, and genes to vitamin D status in Dutch older adults: The B-PROOF study. J Steroid Biochem Mol Biol. 2016;164:168–76.PubMedCrossRef
62.
Findley AS, Zhang X, Boye C, Lin YL, Kalita CA, Barreiro L, Lohmueller KE, Pique-Regi R, Luca F. A signature of Neanderthal introgression on molecular mechanisms of environmental responses. PLoS Genet. 2021;17(9):e1009493.PubMedPubMedCentralCrossRef
Metadata
Title
Association of serum 25-hydroxy-vitamin D concentration and risk of mortality in cancer survivors in the United States
Authors
Xiaofei Mo
Chen He
Fengfeng Han
Hui Yan
Xueqin Chen
Yuetao Wang
Mingge Zhou
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12304-8

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