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Grant Details

Grant Number: 5R03CA119650-02 Interpret this number
Primary Investigator: Wang, Michael
Organization: Harvard School Of Public Health
Project Title: Serum 25(OH)D Levels, Vdr and Cyp24 Polymorphisms, and NSCLC Survival
Fiscal Year: 2007
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Abstract

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer related mortality for both men and women, with an anticipated 174,470 new cases and 162,460 deaths in 2006. Besides quitting or preventing smoking, means to reduce mortality from lung cancer are limited. Recent studies suggested that vitamin D may reduce incidence and diminish progression across a spectrum of cancers including lung cancer. Our preliminary results suggested that the joint effects of surgery season and vitamin D intake are associated with recurrence free survival and overall survival in early stage non-small cell lung cancer (NSCLC) patients. This project will investigate comprehensively the roles of vitamin D in important clinical outcomes of all stages of NSCLC patients. In a large prospectively-collected cohort of NSCLC patients, we will investigate whether higher serum levels of vitamin D (25-hydroxyvitamin D, the primary circulating form of vitamin D) at the time of lung cancer diagnosis/treatment initiation are associated with better prognosis in both early and advanced stage NSCLC patients. We will then investigate the role of polymorphic vitamin D receptor (VDR) and CYP24 genes in altering NSCLC prognosis. Finally, we will study the role of VDR and CYP24 polymorphisms in modifying the association between vitamin D and the NSCLC prognosis. Serum vitamin D levels are measured using radioimmunosorbant assay, dietary and supplement vitamin D intake are obtained using food frequency questionnaires, while candidate polymorphisms are evaluated using PCR-based genotyping techniques. The methods of Kaplan-Meier (logrank tests) and Cox proportional hazards models (adjusting for important covariates) will be used for outcomes analysis. The outcomes of interest for potentially curable early NSCLCs (stage I-IIIA) are recurrence-free survival and overall survival. For advanced NSCLCs (stage IIIB- IV), the outcomes are progression free survival and overall survival. We hope that in accomplishing this project, we will have a better idea of how vitamin D levels at the time of diagnosis/treatment initiation may affect how well a patient does after the diagnosis of lung cancer and how vitamin D may alter the effects of lung cancer treatment. The ultimate goal of this research is to individualize therapies for every patient.

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Publications

Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of Helicobacter pylori infection status.
Authors: Zhai R. , Wei Y. , Su L. , Liu G. , Kulke M.H. , Wain J.C. , Christiani D.C. .
Source: Carcinogenesis, 2015 Jan; 36(1), p. 87-93.
EPub date: 2014-11-08.
PMID: 25381453
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Interactions between environmental factors and polymorphisms in angiogenesis pathway genes in esophageal adenocarcinoma risk: a case-only study.
Authors: Zhai R. , Zhao Y. , Liu G. , Ter-Minassian M. , Wu I.C. , Wang Z. , Su L. , Asomaning K. , Chen F. , Kulke M.H. , et al. .
Source: Cancer, 2012-02-01; 118(3), p. 804-11.
EPub date: 2011-07-12.
PMID: 21751195
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Genetic associations with sporadic neuroendocrine tumor risk.
Authors: Ter-Minassian M. , Wang Z. , Asomaning K. , Wu M.C. , Liu C.Y. , Paulus J.K. , Liu G. , Bradbury P.A. , Zhai R. , Su L. , et al. .
Source: Carcinogenesis, 2011 Aug; 32(8), p. 1216-22.
EPub date: 2011-05-23.
PMID: 21606320
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Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer.
Authors: Heist R.S. , Zhou W. , Wang Z. , Liu G. , Neuberg D. , Su L. , Asomaning K. , Hollis B.W. , Lynch T.J. , Wain J.C. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008-12-01; 26(34), p. 5596-602.
EPub date: 2008-10-20.
PMID: 18936471
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Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk.
Authors: Zhai R. , Liu G. , Asomaning K. , Su L. , Kulke M.H. , Heist R.S. , Nishioka N.S. , Lynch T.J. , Wain J.C. , Lin X. , et al. .
Source: Carcinogenesis, 2008 Dec; 29(12), p. 2330-4.
EPub date: 2008-09-09.
PMID: 18780893
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Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non-small cell lung cancer.
Authors: Zhai R. , Liu G. , Zhou W. , Su L. , Heist R.S. , Lynch T.J. , Wain J.C. , Asomaning K. , Lin X. , Christiani D.C. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2008-01-15; 14(2), p. 612-7.
PMID: 18223238
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Circulating 25-hydroxyvitamin D levels predict survival in early-stage non-small-cell lung cancer patients.
Authors: Zhou W. , Heist R.S. , Liu G. , Asomaning K. , Neuberg D.S. , Hollis B.W. , Wain J.C. , Lynch T.J. , Giovannucci E. , Su L. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2007-02-10; 25(5), p. 479-85.
PMID: 17290055
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Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients.
Authors: Zhou W. , Heist R.S. , Liu G. , Neuberg D.S. , Asomaning K. , Su L. , Wain J.C. , Lynch T.J. , Giovannucci E. , Christiani D.C. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2006 Nov; 15(11), p. 2239-45.
PMID: 17119052
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