VITAMIN D AGAIN

VDR Polymorphisms Linked With Survival in Advanced NSCLC

NEW YORK (Reuters Health) Nov 26 - Researchers who previously showed that polymorphisms in the vitamin D receptor (VDR) gene and serum vitamin D levels may be linked with survival in early-stage non-small cell lung cancer (NSCLC) have now found that some VDR polymorphisms and haplotypes are associated with better survival in advanced NSCLC as well.

In the Journal of Clinical Oncology published online ahead of print on October 20, Dr. David C. Christiani at the Harvard School of Public Health in Boston and colleagues explain that on the basis of their earlier findings, they theorized that "the variant A allele of the Cdx-2 polymorphism, wild-type C allele of the FokI polymorphism, and the variant T allele of the BsmI polymorphism, either individually or combined in joint effects or haplotypes, would be associated with better survival," as would higher circulating levels of vitamin D.

In their study of 294 patients with advanced NSCLC, there was no difference in survival based on circulating vitamin D levels at a median follow-up of 42 months.

There was, however, an association of the C/C genotype of the FokI polymorphism with improved survival. Specifically, the authors report, "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 = 0.005)."

The Cdx-2 and BsmI polymorphisms had no significant impact on survival.

However, there was also an association between improved survival and having increasing numbers of protective alleles, with an adjusted hazard ratio of 0.57 for two or more vs one or no protective alleles.

Also, the authors report that compared to the most common haplotype of G-C-T, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival (adjusted hazard ratio, 1.61). They point out that the G-T-C (Cdx-2-FokI-BsmI) haplotype is thought to have lower VDR activity, whereas the C/C genotype of the FokI polymorphism, which was linked with improved survival, is thought to have higher VDR activity.

"Clinical trials are...investigating the addition of vitamin D or vitamin D analogs to the treatment of patients with various cancers, including lung cancer," the authors note, adding, "Investigating these polymorphisms in these clinical trials will be important for associations with treatment outcomes."