A second genetic variant on chromosome 15q24-25.1 associates with lung cancer

Pengyuan Liu, Ping Yang, Xifeng Wu, Haris G. Vikis, Yan Lu, Yian Wang, Ann G. Schwartz, Susan M. Pinney, Mariza De Andrade, Adi Gazdar, Colette Gaba, Diptasri Mandal, Juwon Lee, Elena Kupert, Daniela Seminara, John Minna, Joan E. Bailey-Wilson, Margaret Spitz, Christopher I. Amos, Marshall W. AndersonMing You

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

A common variant on chromosomal region 15q24-25.1, marked by rs1051730, was found to be associated with lung cancer risk. Here, we attempted to confirm the second variant on 15q24-25.1 in several large sporadic lung cancer populations and determined what percentage of additional risk for lung cancer is due to the genetic effect of the second variant. SNPs rs1051730 and rs481134 were genotyped in 2,818 lung cancer cases and 2,766 controls from four populations. Joint analysis of these two variants (rs1051730 and rs481134) on 15q24-25.1 identified three major haplotypes (G-T, A-C, and G-C) and provided stronger evidence for association of 15q24-25.1 with lung cancer (P = 9.72 x 10-9). These two variants represent three levels of risk associated with lung cancer. The most common haplotype G-T is neutral; the haplotype A-C is associated with increased risk for lung cancer with 5.0% higher frequency in cases than in controls [P = 1.68 x 10-7; odds ratio (OR), 1.24; 95% confidence interval (95% CI), 1.14-1.35]; whereas the haplotype G-C is associated with reduced risk for lung cancer with 4.4% lower frequency in cases than in controls (P = 7.39 x 10-7; OR, 0.80; 95% CI, 0.73-0.87). We further showed that these two genetic variants on 15q24-25.1 independently influence lung cancer risk (rs1051730: P = 4.42 x 10-11; OR, 1.60; 95% CI, 1.46-1.74; rs481134: P = 7.01 x 10-4; OR, 0.81; 95% CI, 0.72-0.92). The second variant on 15q24-25.1, marked by rs481134, explains an additional 13.2% of population attributable risk for lung cancer.

Original languageEnglish (US)
Pages (from-to)3128-3135
Number of pages8
JournalCancer research
Volume70
Issue number8
DOIs
StatePublished - Apr 15 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Liu, P., Yang, P., Wu, X., Vikis, H. G., Lu, Y., Wang, Y., Schwartz, A. G., Pinney, S. M., De Andrade, M., Gazdar, A., Gaba, C., Mandal, D., Lee, J., Kupert, E., Seminara, D., Minna, J., Bailey-Wilson, J. E., Spitz, M., Amos, C. I., ... You, M. (2010). A second genetic variant on chromosome 15q24-25.1 associates with lung cancer. Cancer research, 70(8), 3128-3135. https://doi.org/10.1158/0008-5472.CAN-09-3583