The Role of Vitamin D on the Prognosis and Incidence of Lung Cancer: A Systematic Review and Meta-Analysis

doi:10.21203/rs.3.rs-201134/v1

Download PDF

Research

The Role of Vitamin D on the Prognosis and Incidence of Lung Cancer: A Systematic Review and Meta-Analysis

https://doi.org/10.21203/rs.3.rs-201134/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background: The correlation between vitamin D intake and lung cancer development is controversial. This meta-analysis aims to evaluate the relationship between vitamin D and the prognosis and incidence of lung cancer.

Methods: A comprehensive database search on Pubmed, Web of Science, EBSCO, and Cochrane Library was carried out from the beginning to November 2020. Long-term survival and the incidence rate of patients with lung cancer were the primary outcomes of the study.

Results: Ten eligible studies were selected for the meta-analysis following specific inclusion and exclusion criteria. Four included studies, covering 5007 patients, compared the overall survival (OS) and relapse-free survival (RFS) of lung cancer patients among total vitamin D users with non-users. Significantly, the estimated pooled hazard ratio (HR) revealed that vitamin D could improve OS and RFS of lung cancer patients [HR=0.83, 95% CI (0.72-0.95); HR=0.79, 95% CI (0.61-0.97), respectively]. Vitamin D intake was inversely associated with lung cancer incidence in six studies [OR=0.90, 95% CI (0.83-0.97)].

Conclusions: The present meta-analysis shows vitamin D not only improves the long-term survival of lung cancer patients but has a beneficial effect on the incidence of lung cancer. Notwithstanding, more studies are needed to confirm the study results.

Surgery

Oncology

vitamin D

lung cancer

risk

prognosis

meta-analysis

Lung cancer, with distinct subtypes, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)[1], is a leading cause of cancer incidence and death[2]. In 2018, GLOBOCAN estimated 2.09 million new cases (11.6% of total cancer cases) and 1.76 million deaths (18.4% of total cancer deaths), much higher than reported rates in 2012 (1.8 million new cases and 1.6 million deaths)[1]. Hence, early prevention and diagnosis are incredibly vital to reduce the morbidity and mortality of the disease. Presently, the role of vitamin D has been recognized in several cancers[3, 4], including lung cancer[5].

Vitamin D is principally obtained from three pathways in humans (diet, supplements, and ultraviolet radiation from the sun synthesized on the skin). Additionally, vitamin D supplements usually contain a much higher dose of vitamin D compared to foods[6]. Vitamin D is metabolized to 25-hydroxy vitamin D (25(OH)D) in the liver and further activated by 1-hydroxylase to 1,25-dihydroxyvitamin D (1,25(OH)₂D) in the kidneys. It also accelerates calcium absorption and is connected tightly with bone health[7]. More specifically, the vitamin D receptor (VDR) is a steroid hormone nuclear receptor that regulates a variety of genes within a cell[8]. Vitamin D is hypothesized to prevent cancer relapse by inhibiting cell proliferation, angiogenesis, and metastasis while inducing apoptosis and differentiation[9–13]. Previous studies have reported that vitamin D intake is associated with a decreased risk of different cancers, including prostate[14] and breast[3] cancers, whereas there is no association between vitamin D and cancer types such as esophageal[15], pancreatic[16], skin[17], and gastric[18] cancers. Several observational studies[5, 19] have also investigated the correlation between vitamin D and lung cancer prognosis, but results are not conclusive. However, the effect of vitamin D intake on the incidence of lung cancer remains elusive. For instance, vitamin D was inversely associated with lung cancer incidence in the Carotene and Retinol Efficacy Trial (CARET)[20], but not in the Shanghai Women’s Health Study (SWHS)[21].

Therefore, to address these issues and guide physicians, we conducted a comprehensive meta-analysis using the available data to evaluate the relationship between vitamin D and the prognosis and incidence of lung cancer.

Search strategy

This meta-analysis was conducted per the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement[22]. Two investigators independently assessed the observational studies and the quality of the randomized controlled trials (RCTs) via the Newcastle-Ottawa Quality Assessment Scale (NOS) checklist and the Cochrane Collaborations tool,, respectively. In the meta-analysis, systematic retrieval of databases (Pubmed, Web of Science, EBSCO, and Cochrane Library) was conducted from the beginning to November 2020. The subject search was bonded with free text terms and medical subject headings, including (((‘lung’ OR ‘pulmonary’) AND (‘cancer’ OR ‘carcinoma’ OR ‘adenocarcinoma’ OR ‘squamous carcinoma’ OR ‘neoplasms’)) OR (‘non-small cell lung cancer’ OR ‘small cell lung cancer’ OR ‘NSCLC’ OR ‘SCLC’)) AND (‘vitamin D’). Also, literature references were manually retrieved to avoid omitting relevant studies.

Selection Criteria

Each study retrieved for inclusion was independently assessed by two authors. The inclusion criteria included: (1) studies conducted on human populations, (2) studies including RCTs, cohort, or case-control studies, and (3) reports on the correlation between vitamin D and the prognosis and incidence of lung cancer. Exclusion criteria included: (1) non-original articles, (2) articles with insufficient detailed data and irrelevant outcomes, (3) non-cancer diseases such as lung nodule, and (4) overlapping publications. Significantly, only the most recent, relevant, and comprehensive study was included to avoid duplicates or studies reporting data from the same population in the analysis.

Data Extraction And Study Quality Assessment

Two authors independently completed data extraction and study quality assessment. Uncertainties encountered between the two authors were resolved by consensus or by a third author. Two databases were used to record available information of the literature: a database of the correlation between vitamin D and the prognosis of lung cancer and a database of the correlation between vitamin D and the incidence of lung cancer. These indicators included primarily author(s), year of publication, country, cohort characteristics, sample size, time to recruit, age, follow-up time, vitamin D dose, study design, and adjustment factors.

Statistical analysis

Hazard ratio (HR), including a 95% confidence interval (CI), was used to evaluate the relationship between vitamin D and lung cancer prognosis. Odds ratio (OR), including 95% CI was used to evaluate the correlation between vitamin D and lung cancer incidence. Statistical analyses were conducted via STATA 12.0 Software (Stata, College Station). Cochran’s Q statistic and I² statistics were applied to evaluate heterogeneity in the included studies. A random-effects model was utilized for meta-analysis on account of the variability of vitamin D type and dose. Publication bias was evaluated by Begg’s and Egger’s test, and P < 0.05 was considered statistically significant. Publication bias and sensitivity analysis were not performed on analysis subgroup with less than ten studies because of the low sensitivity of qualitative and quantitative tests[23].

Eligible studies and characteristics

A total of 1086 studies were screened after a database search. Additionally, four studies were identified via other sources. After deleting 329 duplicates, 761 records were browsed through reading article titles and abstracts. Also, 25 studies were evaluated via full-text articles. Finally, ten eligible articles were included in the quantitative synthesis (four studies[5, 19, 24, 25] included the correlation between vitamin D and lung cancer prognosis, while six studies[20, 21, 26–29] included the correlation between vitamin D and the incidence of lung cancer) (Fig. 1). The quality of ten studies was assessed, as shown in Supplementary Table 1.

The characteristics of four studies on the correlation between vitamin D and lung cancer prognosis conducted on lung cancer patients are shown in Table 1Vitamin D intake was from dietary vitamin D and vitamin D supplementation. Adjustment factors were primarily gender, age, alcohol, body mass index, and smoking. Similarly, the characteristics of six studies investigating the correlation between vitamin D and the incidence of lung cancer based on human populations are indicated in Table 2. Total vitamin D intake was from dietary or supplement or both. Adjustment factors were primarily age, education, energy, body mass index, and smoking.

Table 1

Characteristics of all the studies included in the meta-analysis (the correlation between vitamin D and prognosis of lung cancer)
Author	Year	Country	Cohort characteristics	Age, year median (range)	Time to recruit patients	Number of patients	Number of relapses	Number of death	Vit D type	Vit D dose		Median follow-up	Study	Adjustment
Author	Year	Country	Cohort characteristics	Age, year median (range)	Time to recruit patients	Number of patients	Number of relapses	Number of death	Vit D type	Experiment	Control	Median follow-up	Study	Adjustment
Patel	2016	US	The Women’s Health Initiative	50–79	1993	1044	NA	613	Supplementary Vit D	users	non-users	NA	POBS	NA
Zhou	2005	US	Early-Stage Non–Small Cell Lung Cancer Patients	69 (31–89)	1992	456	161	231	Total Vit D Dietary Vit D Supplementary Vit D	≥ 239	< 239	71 mo	POBS	age, gender, stages, retinol
Jeffreys	2015	UK	The UK Clinical Practice Research Datalink	≥ 55	2002	3352	NA	2756	Supplementary Vit D	> 2prescriptions	1–2prescriptions	30.4 mo	POBS	smoking, alcohol, BMI, area-level deprivation
Akiba	2018	Japan	A randomized, double-blind, placebo-controlled study	20–75	2009	77 (vitamin D) 78 (placebo)	NA	NA	Supplementary Vit D	vitamin D	placebo	3.3 yr	RCT	NA
NA, not available; POBS, prospective observational studies; RCT, randomized controlled trial; Vit D, vitamin D; Yr, year; Mo, month; BMI, body mass index.

Table 2

Characteristics of all the studies included in the meta-analysis (the correlation between vitamin D and the incidence of lung cancer)
Author	Year	Country	Cohort characteristics	Time to recruit	Length of follow-up (year)	Age, year median (range)	Follow-up number	Vit D type	Total Vit D dose		Study	Adjustment
Author	Year	Country	Cohort characteristics	Time to recruit	Length of follow-up (year)	Age, year median (range)	Follow-up number	Vit D type	Experiment	Control	Study	Adjustment
Cheng	2013	US	Women’s Health Initiative	1993	17.8	50–79	128779	Total Vit D Dietary Vit D Supplementary Vit D	> 100	< 100	POBS	age, region, race, education, hormone, calcium, BMI, smoking, walking, vitamin A, energy
Takata	2013	China	The Shanghai Women’s Health Study	1997	13	40–70	74941	Total Vit D Dietary Vit D Supplementary Vit D	users	non-users	POBS	age, caloric, income, occupation, smoking, history of asthma, BMI
Redaniel	2014	UK	The UK Clinical Practice Research Datalink	2002	8	≥ 55	484	Supplementary Vit D	> 2 prescriptions	1–2 prescriptions	ROBS	NA
Cheng	2014	NA	The Carotene and Retinol Efficacy Trial	1988	17.8	50–69(women) 45–69(men)	14254 (women) 4060 (men)	Total Vit D Dietary Vit D Supplementary Vit D	> 200	< 200	ROBS	age, study center, race, education, asbestos exposure worker, trade, smoking, BMI, energy, vitamin A
Lappe	2017	US	A double-blind, placebo-controlled, population-based randomized clinical trial	2009	6	65.2	1102 (vitamin D + Ca) 1095 (placebo)	Supplementary Vit D	vitamin D + Ca	placebo	RCT	NA
Lappe	2007	US	A double-blind, placebo-controlled, population-based randomized clinical trial	2003	4	≥ 55	1179	Supplementary Vit D	vitamin D + Ca	Ca	RCT	NA
								Supplementary Vit D	vitamin D + Ca	placebo
NA, not available; RCT, randomized controlled trial; ROBS, retrospective observational study; POBS, prospective observational study; Vit D, vitamin D; BMI, body mass index

Vitamin D And Lung Cancer Prognosis

Four studies, covering 5007 people, were included in the analysis to compare the overall survival (OS) of lung cancer patients between vitamin D users and non-vitamin D users (high intake and low intake). The estimated pooled HR revealed that the use of vitamin D could improve the OS of lung cancer patients [HR = 0.83, (0.72–0.95)] (Fig. 2). Only two studies were utilized to compare the relapse-free survival (RFS) of lung cancer between vitamin D users and non-vitamin D users (high intake and low intake). According to the estimated pooled HR, vitamin D intake significantly improved the RFS of lung cancer patients [HR = 0.79, (0.61–0.97)](Fig. 3).

Vitamin D And Incidence Of Lung Cancer

Six studies, covering 225894 people, reported OR of lung cancer among vitamin D high intake compared with low intake. Additionally, there was no heterogeneity (I² = 0%). Due to the variability of vitamin D type and dose, a random-effects model was applied to the meta-analysis. The estimated pooled OR of lung cancer for high intake versus low intake of total vitamin D was 0.90 (95%CI: 0.83–0.97), indicating an association between increased total vitamin D intake and a small reduction in the risk of lung cancer (Fig. 4).

Publication Bias And Sensitivity Analysis

Considering that these studies selected were less than ten, Begg’s and Egger’s tests for publication bias and sensitivity analysis were not used for the meta-analysis due to the low efficiency of qualitative and quantitative tests.

In the study, we conducted a comprehensive meta-analysis on ten articles. Four articles evaluated the correlation between vitamin D and lung cancer prognosis, while six articles examined the correlation between vitamin D and lung cancer risk. Significantly, vitamin D intake was related to a decline in lung cancer risk and an improved long-term prognosis in lung cancer patients. The relatively few relevant studies that observed the relationship between vitamin D intake and lung cancer prognosis and lung cancer incidence limited our ability to conduct subgroup analyses.

Vitamin D intake is derived from diet, supplements, and ultraviolet radiation from the sun synthesized on the skin. 1,25(OH)₂D may exert its anticarcinogenic effects via stimulating the secretion of protein glues, such as E-cadherin and catenin, which make cells more adherent to each other[19]. It reduces the possible mobilization of several malignant cells into the lymphatic or blood circulation, invariably delaying lung cancer progression. Besides, 1,25(OH)₂D inhibits the expression of cyclooxygenase-2 and prostaglandin synthesis, which can contribute to cancer cell growth and angiogenesis[30].

Vitamin D enhances the transcription of cathelicidin antimicrobial peptide genes, and the translation of CD14, a co-receptor for recognizing bacterial lipopolysaccharides. Both immensely improve the host body defense and are essential for congenital immunity[31]. The anticarcinogenic role of 1,25(OH)₂D in regulating cell proliferation and angiogenesis are relevant to lung tumorigenesis. 1,25(OH)₂D inhibits lung cancer signaling pathways, including mutations in epidermal growth factor receptor, Wnt-β-catenin dysregulation, and vascular endothelial growth factor[9, 32].

Moreover, vitamin D promotes G1 cell-cycle arrest through signaling cyclin-dependent kinase inhibitors p21 and p27[33]. Both p21 and p27 proteins closely co-function with the ras oncogene family[34, 35], and K-ras often mutate in adenocarcinoma[36]. Further, human lung tumor cell lines and animal experiments have demonstrated that the active metabolite of 25(OH)D—1,25(OH)₂D suppresses angiogenesis and cancer cell growth by inhibiting the response to vascular endothelial growth factor[37].

The meta-analysis indicated that vitamin D intake could improve the long-term survival of lung cancer patients. A previous meta-analysis reported no significant association between blood vitamin D levels and lung cancer survival[38]. The study results above might be related to the vitamin D concentrations, which were too low (average value = 17.7 ng/ml) to observe any significant impact on the prognosis. Clinically, vitamin D levels below 20 ng/ml are considered deficient[39]. Besides, the disease stage was likely too advanced among patients selected for vitamin D levels to influence prognosis.

It is worth noting that these studies focusing on serum levels of vitamin D on lung cancer progression might not be directly comparable to vitamin D intake. Vitamin D intake might not correlate with vitamin D levels, since sun exposure, dietary vitamin D, and supplementation source affect vitamin D serum levels. Nevertheless, vitamin D from sun exposure is limited in some countries situated above the latitude. Moreover, older patients have reduced dermal capacity to synthesize vitamin D and spend relatively large amounts of time indoors, while younger adults are more likely to use sun creams outdoors. In comparison, the present meta-analysis is the first to investigate the correlation between vitamin D and lung cancer prognosis.

Notably, two cohort studies^5, [19] reported that vitamin D intake could significantly improve lung cancer patients’ OS. However, the Women’ s Health Initiative indicated that vitamin D has little effort on the OS of lung cancer patients[24]. Indeed, there is evidence that estrogens might play a role in lung adenocarcinoma in women[40]. Findings suggesting that estrogen receptors are present in lung tumors; however, playing a role in the activation of vitamin D and its receptor expression are provocative and warrant further exploration[41].

Simultaneously, two studies by Zhou et al.[19] and Akiba et al.[25] were conflicting because the former highlighted that vitamin D intake could significantly improve the RFS of lung cancer patients, whereas the latter did not corroborate the result. Collectively, the present meta-analysis concludes that increased vitamin D intake could improve the prognosis of lung cancer patients. Thus, further research and more evidence are needed to prove if vitamin D intake can influence lung cancer prognosis. A meta-analysis showed the inverse correlation between dietary vitamin D intake and lung cancer hazard, which was not investigated further if total vitamin D intake has a protective effect on lung cancer hazard[42]. Although another meta-analysis, which included only three RCTs, suggested that vitamin D intake cannot play a significant role in lung cancer[43]. In contrast, the present study showed that total vitamin D intake can protect against lung cancer occurrence. Therefore, it is pertinent to investigate further the correlation between total vitamin D intake and lung cancer risk.

Based on the strata of cohort studies, a study by Cheng et al.[20] compared high and low vitamin D intake found a negative association between vitamin D intake and lung cancer. However, it was discrepant with a report[28] by Redaniel et al.. The contradicting results between Redaniel et al.[28] and other studies[20, 27] probably could be due to the different vitamin D intake sources, with the latter studies, including the dietary intake of vitamin D[20, 27].

Moreover, the present trial showed that the total vitamin D intake has no protective effect on lung cancer incidence, which was likely because the present trial did not separate calcium from vitamin D influence on lung cancer, as these agents were simultaneously used in the study[29]. An RCT by Lappe et al. comparing Calcium (Ca) plus vitamin D supplementation and Ca supplementation suggested that vitamin D intake was associated with a decreased lung cancer risk. Herein, the present study result demonstrated that vitamin D intake protects against the risk of lung cancer[26].

Dietary supplements should be supplemented with foods containing vitamin D, such as deep-sea fish and animal liver. However, it is not enough for individuals vulnerable to vitamin D deficiency to only get vitamin D from their daily diet. Therefore, it is recommended to consider vitamin D nutritional supplementation. The Institute of Medicine (IOM) recommended 400 IU daily for children under one year of age, 600 IU daily for children one year and older and older adults between the ages of 70 years, and 800 IU daily for adults over 70 years of age, to achieve a blood level of at least 20ng/mL.

The Endocrine Society recommends a daily dose of 400–1000 IU for children under one year of age, 600–1000 IU for children one year and older, and a 1500–2000 IU daily dose for all adults to sustain a circulating serum level of 25(OH)D > 30ng/mL[39]. Nonetheless, more studies are needed to confirm these suggestions to regulate the safety range better. Though the safe dose range of vitamin D is vast, intoxication, or other harmful events following vitamin D intake must be considered. Notably, the dose-response relation was not consistent. Thus, the optimal dose of vitamin D usage still needs to be evaluated further via large-scale studies. Therefore, to delay cancer progression and reduce lung cancer risk, individuals are advised to take vitamin D supplements in conjunction with a healthy lifestyle.

Study strengths: To our knowledge, the study herein is the first comprehensive meta-analysis investigating the role between vitamin D intake and the prognosis of lung cancer patients. Besides, the present meta-analysis contains relatively more comprehensive studies for investigating vitamin D’s effect on the hazard of lung cancer, thereby updating and extending previous results to provide more robust support.

Significantly, the meta-analysis herein has few inherent potential limitations that should be taken into account. Firstly, vitamin D dose categories varied among the included studies, which was an inherent bias in the quantitative assessment. Secondly, even though we attempted to carry out a literature search as comprehensively as possible, we could not acquire unpublished articles, and the language was merely confined to English. Finally, the included studies were nonetheless limited. Hence, we could not carry out sensitivity analysis on possible publication bias, which might have influenced the study conclusions. Therefore, the present study results should be interpreted with caution.

The meta-analysis herein shows that vitamin D intake can improve the prognosis of lung cancer patients. Additionally, vitamin D intake is inversely linked with the incidence of lung cancer. Notwithstanding, the meta-analysis herein still requires well-designed large-scale observational studies and RCTs to confirm the study results. Meanwhile, there is a need to lengthen the duration of follow-up and evaluate the optimal dosing of vitamin D usage.

NSCLC,non small cell lung cancer; SCLC, small cell lung cancer; CARET, the Carotene and Retinol Efficacy Trial; SWHS, the Shanghai Women’s Health Study; OR, odds ratio; HR, hazard radio; OS, overall survival; RFS, relapse-free survival; CI, confidence interval; RCT, randomized controlled trial; BMI, body mass index; IOM, The Institute of Medicine; NOS, Newcastle-Ottawa Quality Assessment Scale; PRISMA-P, Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols; VDR, vitamin D receptor; 1,25(OH)₂D, 1,25-dihydroxyvitamin D; 25(OH)D, 25-hydroxy vitamin D

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Funding

The authors have no financial support to declare.

Competing interests

The authors declare that they have no conflict of interest.

Availability of data and materials

The datasets supporting the conclusions of this article are included within the article.

Authors’ contributions

LLQ designed the research process. DG and MXQ searched the database for corresponding articles. SPQ and XJF extracted useful information from the articles above. RRF used statistical software for analysis. LLY drafted the meta-analysis. DG and MXQ polished this article. All authors had read and approved the manuscript and ensured that this was the case.

Acknowledgements

Not applicable.

Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020;383(7):640–9.
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.
Hossain S, Beydoun M, Beydoun H, Chen X, Zonderman A, Wood RJCnE. Vitamin D and breast cancer: A systematic review and meta-analysis of observational studies. 2019, 30:170–184.
Shahvazi S, Soltani S, Ahmadi S, de Souza R, Salehi-Abargouei AJH. metabolisme mrH-uSHe: The Effect of Vitamin D Supplementation on Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials. 2019, 51(1):11–21.
Jeffreys M, Redaniel M, Martin RJBc. The effect of pre-diagnostic vitamin D supplementation on cancer survival in women: a cohort study within the UK Clinical Practice Research Datalink. 2015, 15:670.
McKenna M, Murray BJEc. Vitamin D dose response is underestimated by Endocrine Society's Clinical Practice Guideline. 2013, 2(2):87–95.
Zerwekh, JJTAjocn. Blood biomarkers of vitamin D status. 2008, 87(4):1087S-1091S.
Lei M, Liu Z, Guo JJBri: The Emerging Role of Vitamin D and Vitamin D Receptor in Diabetic Nephropathy. 2020, 2020:4137268.
Deeb K, Trump D, Johnson CJNrC. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. 2007, 7(9):684–700.
Hanahan D, Weinberg RJC. Hallmarks of cancer: the next generation. 2011, 144(5):646–674.
Díaz G, Paraskeva C, Thomas M, Binderup L, Hague AJCr. Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. 2000, 60(8):2304–2312.
Fernandez-Garcia N, Palmer H, Garcia M, Gonzalez-Martin A, del Rio M, Barettino D, Volpert O, Muñoz A, Jimenez BJO. 1alpha,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells. 2005, 24(43):6533–6544.
Evans S, Shchepotin E, Young H, Rochon J, Uskokovic M, Shchepotin IJIjoo: 1,25-dihydroxyvitamin D3 synthetic analogs inhibit spontaneous metastases in a 1,2-dimethylhydrazine-induced colon carcinogenesis model. 2000, 16(6):1249–1254.
Gilbert R, Martin R, Beynon R, Harris R, Savovic J, Zuccolo L, Bekkering G, Fraser W, Sterne J, Metcalfe CJCc et al: Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. 2011, 22(3):319–340.
Zgaga L, O'Sullivan F, Cantwell M, Murray L, Thota P, Coleman HJCe, biomarkers, prevention: a publication of the American Association for Cancer Research cbtASoPO: Markers of Vitamin D Exposure and Esophageal Cancer Risk: A Systematic Review and Meta-analysis. 2016, 25(6):877–886.
Zhang X, Huang X, Chen W, Wu J, Chen Y, Wu C, Wang ZJO: Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis. 2017, 8(38):64395–64406.
Mahamat-Saleh Y, Aune D, Schlesinger SJSr. 25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies. 2020, 10(1):13151.
Khayatzadeh S, Feizi A, Saneei P, Esmaillzadeh AJJorimstojoIUoMS: Vitamin D intake, serum Vitamin D levels, and risk of gastric cancer: A systematic review and meta-analysis. 2015, 20(8):790–796.
Zhou W, Suk R, Liu G, Park S, Neuberg D, Wain J, Lynch T, Giovannucci E. Christiani DJCe, biomarkers, prevention: a publication of the American Association for Cancer Research cbtASoPO: Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. 2005, 14(10):2303–2309.
Cheng T, Goodman G, Thornquist M, Barnett M, Beresford S, LaCroix A, Zheng Y, Neuhouser MJIjoc. Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers. 2014, 135(9):2135–2145.
Takata Y, Shu X, Yang G, Li H, Dai Q, Gao J, Cai Q, Gao Y. Zheng WJCe, biomarkers, prevention: a publication of the American Association for Cancer Research cbtASoPO: Calcium intake and lung cancer risk among female nonsmokers: a report from the Shanghai Women's Health Study. 2013, 22(1):50–57.
Gu L, Khadaroo P, Chen L, Li X, Zhu H, Zhong X, Pan J, Chen MJJogsojotSfSotAT: Comparison of Long-Term Outcomes of Endoscopic Submucosal Dissection and Surgery for Early Gastric Cancer: a Systematic Review and Meta-analysis. 2019, 23(7):1493–1501.
Ioannidis J, Trikalinos TJCCMAjjdlAmc. The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. 2007, 176(8):1091–1096.
Patel M, Wang A, Kapphahn K, Desai M, Chlebowski R, Simon M, Bird C, Corbie-Smith G, Gomez S, Adams-Campbell L, et al: Racial and Ethnic Variations in Lung Cancer Incidence and Mortality: Results From the Women's Health Initiative. 2016, 34(4):360–368.
Akiba T, Morikawa T, Odaka M, Nakada T, Kamiya N, Yamashita M, Yabe M, Inagaki T, Asano H, Mori S, et al: Vitamin D Supplementation and Survival of Patients with Non-small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial. 2018, 24(17):4089–4097.
Lappe J, Travers-Gustafson D, Davies K, Recker R, Heaney RJTAjocn. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. 2007, 85(6):1586–1591.
Cheng T, Lacroix A, Beresford S, Goodman G, Thornquist M, Zheng Y, Chlebowski R, Ho G. Neuhouser MJTAjocn: Vitamin D intake and lung cancer risk in the Women's Health Initiative. 2013, 98(4):1002–1011.
Redaniel M, Gardner M, Martin R, Jeffreys, MJCc. CCC c: The association of vitamin D supplementation with the risk of cancer in postmenopausal women. 2014, 25(2):267–271.
Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SJJ. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. 2017, 317(12):1234–1243.
Krishnan A, Swami S, Peng L, Wang J, Moreno J, Feldman DJE. Tissue-selective regulation of aromatase expression by calcitriol: implications for breast cancer therapy. 2010, 151(1):32–42.
Hansdottir S, Monick M, Hinde S, Lovan N, Look D. Hunninghake GJJoi: Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. 2008, 181(10):7090–7099.
Königshoff M. Eickelberg OJAjorc, biology m: WNT signaling in lung disease: a failure or a regeneration signal? 2010, 42(1):21–31.
Hershberger P, Modzelewski R, Shurin Z, Rueger R, Trump D. Johnson CJCr: 1,25-Dihydroxycholecalciferol (1,25-D3) inhibits the growth of squamous cell carcinoma and down-modulates p21(Waf1/Cip1) in vitro and in vivo. 1999, 59(11):2644–2649.
Tanaka T, Slamon D, Battifora H, Cline MJCr. Expression of p21 ras oncoproteins in human cancers. 1986, 46(3):1465–1470.
Serres M, Zlotek-Zlotkiewicz E, Concha C, Gurian-West M, Daburon V, Roberts J, Besson AJO. Cytoplasmic p27 is oncogenic and cooperates with Ras both in vivo and in vitro. 2011, 30(25):2846–2858.
Herbst R, Heymach J, Lippman SJTNEjom. Lung cancer. 2008, 359(13):1367–1380.
Torre L, Siegel R. Jemal AJAiem, biology: Lung Cancer Statistics. 2016, 893:1–19.
Liu J, Dong Y, Lu C, Wang Y, Peng L, Jiang M, Tang Y, Zhao QJO. Meta-analysis of the correlation between vitamin D and lung cancer risk and outcomes. 2017, 8(46):81040–81051.
Holick MJJoc. endocrinology t: Cancer, sunlight and vitamin D. 2014, 1(4):179–186.
Taioli E, Wynder EJJotNCI. Re: Endocrine factors and adenocarcinoma of the lung in women. 1994, 86(11):869–870.
Welsh J, Wietzke J, Zinser G, Byrne B, Smith K. Narvaez CJTJon: Vitamin D-3 receptor as a target for breast cancer prevention. 2003, 133:2425S-2433S.
Wei H, Jing H, Wei Q, Wei G, Heng ZJM: Associations of the risk of lung cancer with serum 25-hydroxyvitamin D level and dietary vitamin D intake: A dose-response PRISMA meta-analysis. 2018, 97(37):e12282.
Cortés-Jofré M, Rueda J, Asenjo-Lobos C, Madrid E, Bonfill Cosp XJTCdosr: Drugs for preventing lung cancer in healthy people. 2020, 3:CD002141.

SupplementaryTable1.docx
Supplementary Table 1. Quality assessment of the enrolled studies.

Download PDF

Version 1

posted

You are reading this latest preprint version

The Role of Vitamin D on the Prognosis and Incidence of Lung Cancer: A Systematic Review and Meta-Analysis

Status:

Version 1

Abstract

Figures

Background

Methods

Search strategy

Selection Criteria

Data Extraction And Study Quality Assessment

Statistical analysis

Results

Eligible studies and characteristics

Vitamin D And Lung Cancer Prognosis

Vitamin D And Incidence Of Lung Cancer

Publication Bias And Sensitivity Analysis

Discussion

Conclusion

Abbreviations

Declarations

References

Supplementary Files

Status:

Version 1