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Liu, Zhiwei; Goldstein, Alisa M.; Hsu, Wan-Lun; Yu, Kelly J.; Chien, Yin-Chu; Ko, Jenq-Yuh; Jian, James Jer-Min; Tsou, Yung-An; Leu, Yi-Shing; Liao, Li-Jen; Chang, Yen-Liang; Wang, Cheng-Ping; Wu, Jia-Shing; Hua, Chun-Hung; Lee, Jehn-Chuan; Yang, Tsung-Lin; Hsiao, Chuhsing Kate; Wu, Ming-Shiang; Tsai, Ming-Hsui; Huang, Kuei-Kang; Yu, Kai; Jones, Kristie; Zhu, Bin; Yeager, Meredith; [...]

Evaluation of Rare and Common Variants from Suspected Familial or Sporadic Nasopharyngeal Carcinoma (NPC) Susceptibility Genes in Sporadic NPC

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  • Media type: E-Article
  • Title: Evaluation of Rare and Common Variants from Suspected Familial or Sporadic Nasopharyngeal Carcinoma (NPC) Susceptibility Genes in Sporadic NPC
  • Contributor: Liu, Zhiwei; Goldstein, Alisa M.; Hsu, Wan-Lun; Yu, Kelly J.; Chien, Yin-Chu; Ko, Jenq-Yuh; Jian, James Jer-Min; Tsou, Yung-An; Leu, Yi-Shing; Liao, Li-Jen; Chang, Yen-Liang; Wang, Cheng-Ping; Wu, Jia-Shing; Hua, Chun-Hung; Lee, Jehn-Chuan; Yang, Tsung-Lin; Hsiao, Chuhsing Kate; Wu, Ming-Shiang; Tsai, Ming-Hsui; Huang, Kuei-Kang; Yu, Kai; Jones, Kristie; Zhu, Bin; Yeager, Meredith; [...]
  • Published: American Association for Cancer Research (AACR), 2019
  • Published in: Cancer Epidemiology, Biomarkers & Prevention, 28 (2019) 10, Seite 1682-1686
  • Language: English
  • DOI: 10.1158/1055-9965.epi-19-0007
  • ISSN: 1055-9965; 1538-7755
  • Origination:
  • Footnote:
  • Description: Abstract Background: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC. Methods: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case–control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted. Results: We found that NPC was associated with combined common and rare variants in CDKN2A/2B (P = 1.3 × 10−4), BRD2 (P = 1.6 × 10−3), TNFRSF19 (P = 4.0 × 10−3), and CLPTM1L/TERT (P = 5.4 × 10−3). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10−4; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU (P = 3.8 × 10−3) for NPC risk. In addition, we validated four previously reported NPC risk–associated SNPs. Conclusions: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC. Impact: NPC-associated genes, including CLPTM1L/TERT, BRD2, and HNRNPU, suggest a role for telomere length maintenance in NPC etiology.
  • Access State: Open Access