Originally published as JCO Early Release 10.1200/JCO.2008.18.0406 on October 20 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Heist, R. S. Articles by Christiani, D. C. Search for Related Content PubMed PubMed Citation Articles by Heist, R. S. Articles by Christiani, D. C. Social Bookmarking                            What's this?

Circulating 25-Hydroxyvitamin D, VDR Polymorphisms, and Survival in Advanced Non–Small-Cell Lung Cancer

Rebecca Suk Heist, Wei Zhou, Zhaoxi Wang, Geoffrey Liu, Donna Neuberg, Li Su, Kofi Asomaning, Bruce W. Hollis, Thomas J. Lynch, John C. Wain, Edward Giovannucci, David C. Christiani

From the Massachusetts General Hospital; Harvard School of Public Health, Boston, MA; Princess Margaret Hospital, Toronto, Ontario, Canada; and Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC

Corresponding author: David C. Christiani, MD, MPH, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115; e-mail: dchris{at}hsph.harvard.edu

Purpose We showed previously that in early-stage non–small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC.

Patients and Methods We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G>A (rs11568820), FokI C>T (rs10735810), and BsmI C>T (rs144410); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status.

Results There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001).

Conclusion There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR FokI>T polymorphism and the G-T-C (Cdx-2-FokI-BsmI) haplotype were associated with worse survival.

published online ahead of print at www.jco.org on October 20, 2008.

Supported by National Institutes of Health Grants No. CA074386, CA092824, CA090578, CA119650, and K12CA087723; American Institute for Cancer Research; and Flight Attendants Medical Research Institute Young Clinical Scientist Award.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?