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. 2013 Nov;34(11):2525-30.
doi: 10.1093/carcin/bgt244. Epub 2013 Jul 9.

TNFRSF10B polymorphisms and haplotypes associated with increased risk of death in non-small cell lung cancer

Matthew B Schabath  1 , Anna R Giuliano, Zachary J Thompson, Ernest K Amankwah, Jhanelle E Gray, David A Fenstermacher, Kristen A Jonathan, Amer A Beg, Eric B Haura
Affiliations

TNFRSF10B polymorphisms and haplotypes associated with increased risk of death in non-small cell lung cancer

Matthew B Schabath et al. Carcinogenesis. 2013 Nov.

Abstract

Presently, there are few validated biomarkers that can predict survival or treatment response for non-small cell lung cancer (NSCLC) and most are based on tumor markers. Biomarkers based on germ line DNA variations represent a valuable complementary strategy, which could have translational implications by subclassifying patients to tailored, patient-specific treatment. We analyzed single nucleotide polymorphisms (SNPs) in 53 inflammation-related genes among 651 NSCLC patients. Multivariable Cox proportional hazard models, adjusted for lung cancer prognostic factors, were used to assess the association of genotypes and haplotypes with overall survival. Four of the top 15 SNPs associated with survival were located in the TNF-receptor superfamily member 10b (TNFRSF10B) gene. The T-allele of the top ranked SNP (rs11785599) was associated with a 41% increased risk of death (95% confidence interval [CI] = 1.16-1.70) and the other three TNFRSF10B SNPs (rs1047275, rs4460370 and rs883429) exhibited a 35% (95% CI = 1.11-1.65), 29% (95% CI = 1.06-1.57) and 24% (95% CI = 0.99-1.54) increased risk of death, respectively. Haplotype analyses revealed that the most common risk haplotype (TCTT) was associated with a 78% (95% CI = 1.25-2.54) increased risk of death compared with the low-risk haplotype (CGCC). When the data were stratified by treatment, the risk haplotypes exhibited statistically significantly increased risk of death among patients who had surgery only and no statistically significant effects among patients who had surgery and adjuvant chemotherapy. These data suggest that possessing one or more risk alleles in TNFRSF10B is associated with an increased risk of death. Validated germ line biomarkers may have potential important clinical implications by optimizing patient-specific treatment.

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Figures

Fig. 1.
Fig. 1.
Kaplan–Meier survival curves for the four TNFRSF10B SNPs. The common genotype for each SNP was set as the referent for all analyses.
Fig. 2.
Fig. 2.
Kaplan–Meier plot for the TNFRSF10B haplotypes using the low-risk haplotype (CGCC) as the referent.
See this image and copyright information in PMC

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