Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients.
Our previous analysis suggested that surgery season in the summer time and high vitamin D intake are associated with improved survival in early-stage non-small cell lung cancer (NSCLC) patients. Here, we investigated the associations of vitamin D receptor (VDR) polymorphisms of Cdx-2 G>A, FokI C>T, and BsmI C>T with overall survival (OS) and recurrence-free survival (RFS) in 373 early-stage NSCLC patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median follow-up time was 71 months (range, 0.1-140 months), with 186 deaths and 127 recurrences. There was no association between VDR polymorphisms and survival, overall or among adenocarcinoma patients. Among squamous cell carcinoma (SCC) patients, the G/A+A/A genotype group of the Cdx-2 polymorphism was associated with better OS: the 5-year OS rates were 41% [95% confidence interval (95% CI), 28-53] for the G/G and 55% (95% CI, 39-71) for the G/A+A/A genotypes, respectively (P = 0.04, log-rank test), with the adjusted hazard ratio of 0.56 (95% CI, 0.33-0.95) for G/A+A/A versus G/G. For the joint effects of the three polymorphisms, subjects with two or more "protective" alleles have better OS among SCC patients, with the adjusted hazard ratios of 0.20 (95% CI, 0.09-0.48), 0.40 (95% CI, 0.19-0.87), and 0.43 (95% CI, 0.19-0.97), respectively, for subjects with two, three, and four or more "protective" alleles when compared with subjects with zero or one "protective" allele (P(trend) = 0.71). Similar associations were found in haplotype analysis and for RFS among SCC patients. In conclusion, VDR polymorphisms may be associated with improved survival among SCC patients of early-stage NSCLC.
Zhou
Wei
W
Departments of Environmental Health, Occupational Health Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. wzhou@hsph.harvard.edu
Heist
Rebecca S
RS
Liu
Geoffrey
G
Neuberg
Donna S
DS
Asomaning
Kofi
K
Su
Li
L
Wain
John C
JC
Lynch
Thomas J
TJ
Giovannucci
Edward
E
Christiani
David C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000378:metabolism
D018167:Receptors, Calcitriol; D014807:Vitamin D