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J Clin Oncol. 2009 Jun 1;27(16):2660-7. doi: 10.1200/JCO.2008.18.7906. Epub 2009 May 4.

Genome-wide analysis of survival in early-stage non-small-cell lung cancer.

Author information

1
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.

Abstract

PURPOSE:

Lung cancer, of which 85% is non-small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC.

PATIENTS AND METHODS:

One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival.

RESULTS:

Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P < or = 2.5 x 10(-4)) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (P(trend) = 3.80 x 10(-12) and 2.48 x 10(-7) for MGH and Norwegian cohorts, respectively).

CONCLUSION:

Five SNPs were identified that may be prognostic of overall survival in early-stage NSCLC.

PMID:
19414679
PMCID:
PMC2690391
DOI:
10.1200/JCO.2008.18.7906
[Indexed for MEDLINE]
Free PMC Article

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