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 performed on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital in Boston, MA, USA.
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 (GWAS), 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.
Authors: Hu L, Wu C, Zhao X, Heist RS, Su L, Zhao Y, Han B, Cao S, Chu M, Dai J, Dong J, Shu Y, Xu L, Chen Y, Wang Y, Lu F, Jiang Y, Yu D, Chen H, Tan W, Ma H, Chen J, Jin G, Wu T, Lu D, Christiani DC, Lin D, Hu Z, Shen H
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