Genome-wide association study of prognosis in advanced non-small cell lung cancer patients receiving platinum-based chemotherapy

Clin Cancer Res. 2012 Oct 1;18(19):5507-14. doi: 10.1158/1078-0432.CCR-12-1202. Epub 2012 Aug 7.

Abstract

Purpose: Genetic variation may influence chemotherapy response and overall survival in cancer patients.

Experimental design: We conducted a genome-wide scan in 535 advanced-stage non-small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA).

Results: Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10(-5) to 4.19 × 10(-7) in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population.

Conclusion: In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cisplatin / administration & dosage
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis*
  • Survival Analysis
  • White People / genetics
  • beta Catenin / genetics*

Substances

  • CTNNB1 protein, human
  • beta Catenin
  • Carboplatin
  • Cisplatin