Thoracic Cancer (Jan 2020)

Polymorphism in ASCL1 target gene DDC is associated with clinical outcomes of small cell lung cancer patients

  • Ji Hyun Kim,
  • Shin Yup Lee,
  • Jin Eun Choi,
  • Sook Kyung Do,
  • Jang Hyuck Lee,
  • Mi Jeong Hong,
  • Hyo‐Gyoung Kang,
  • Won Kee Lee,
  • Kyung Min Shin,
  • Ji Yun Jeong,
  • Sun Ha Choi,
  • Yong Hoon Lee,
  • Hyewon Seo,
  • Seung Soo Yoo,
  • Jaehee Lee,
  • Seung Ick Cha,
  • Chang Ho Kim,
  • Jae Yong Park

DOI
https://doi.org/10.1111/1759-7714.13212
Journal volume & issue
Vol. 11, no. 1
pp. 19 – 28

Abstract

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Background Achaete‐scute homolog 1 (ASCL1) is a basic helix‐loop‐helix transcription factor and is essential in the differentiation of neuroendocrine cells and neural tissues. ASCL1 is frequently overexpressed in small cell lung cancer (SCLC) and plays a crucial role in the pathogenesis of SCLC. Methods This study was conducted to identify the association between single nucleotide polymorphisms (SNPs) in ASCL1 target genes and clinical outcomes of patients with SCLC after chemotherapy. A total of 261 patients diagnosed with SCLC were enrolled in this study. The association between 103 SNPs in 58 ASCL1 target genes and the response to chemotherapy and survival of patients with SCLC were analyzed. Results Among the 103 SNPs, 10 SNPs were significantly associated with the response to chemotherapy, and 19 SNPs were associated with OS in multivariate analyses. Among these, Dopa Decarboxylase (DDC) rs12666409A>T was significantly associated with both a worse response to chemotherapy and worse OS (adjusted odds ratio [aOR] = 0.40, 95% CI = 0.18–0.90, P = 0.03; adjusted hazard ratio [aHR] = 1.52, 95% CI = 1.10–2.10, P = 0.01, respectively, under a dominant model). In a stage‐stratified analysis, the association was significant only in the extensive disease subgroup (aOR = 0.19, 95% CI = 0.06–0.60, P = 0.01; aHR = 1.73, 95% CI = 1.16–2.56, P = 0.01, respectively, under a dominant model), but not in the limited disease subgroup. Conclusion The results of our study suggest that DDC rs12666409A>T may be useful markers for predicting the clinical outcomes of patients with SCLC undergoing chemotherapy.

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