TNFRSF10B polymorphisms and haplotypes associated with increased risk of death in non-small cell lung cancer
| Autor: | Eric B. Haura, David Fenstermacher, Anna R. Giuliano, Kristen A. Jonathan, Zachary J. Thompson, Jhanelle E. Gray, Ernest K. Amankwah, Matthew B. Schabath, Amer A. Beg |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Original Manuscript Single-nucleotide polymorphism Adenocarcinoma Biology Polymorphism Single Nucleotide Carcinoma Non-Small-Cell Lung Internal medicine Genotype Biomarkers Tumor medicine Humans Prospective Studies Lung cancer Prospective cohort study Survival rate Neoplasm Staging Tumor marker Haplotype General Medicine Adenocarcinoma Bronchiolo-Alveolar Middle Aged Prognosis medicine.disease Survival Rate Receptors TNF-Related Apoptosis-Inducing Ligand Haplotypes Immunology Carcinoma Squamous Cell Carcinoma Large Cell Female Follow-Up Studies |
| Zdroj: | Carcinogenesis. 34:2525-2530 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgt244 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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