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Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival.

Publication ,  Journal Article
Li, H; Wang, Y; Liu, H; Shi, Q; Xu, Y; Wu, W; Zhu, D; Amos, CI; Fang, S; Lee, JE; Han, J; Wei, Q
Published in: Int J Cancer
March 15, 2017

To identify genetic variants involved in prognosis of cutaneous melanoma (CM), we investigated associations of single nucleotide polymorphisms (SNPs) of genes in the integrin signaling pathway with CM survival by re-analyzing a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center (MDACC) and then validated significant SNPs in another GWAS from Harvard University. In the MDACC study, 1,148 SNPs were significantly associated with CM-specific survival (CMSS) (p ≤ 0.050 and false-positive report probability ≤ 0.20), and nine SNPs were validated in the Harvard study (p ≤ 0.050). Among these, three independent SNPs (i.e., DOCK1 rs11018104 T > A, rs35748949 C > T and PAK2 rs1718404 C > T) showed a predictive role in CMSS, with an effect-allele attributed adjusted hazards ratio [adjHR of 1.50 (95% confidence interval (CI) = 1.18-1.90, p = 7.46E-04), 1.53 (1.18-1.97, 1.18E-03) and 0.58 (0.45-0.76, 5.60E-05), respectively]. Haplotype analysis revealed that a haplotype carrying two risk alleles A-T in DOCK1 was associated with the poorest survival in both MDACC (adjHR = 1.73, 95% CI = 1.19-2.50, p = 0.004) and Harvard (adjHR = 1.95, 95% CI = 1.14-3.33, p = 0.010) studies. In addition, patients with an increasing number of unfavorable genotypes (NUGs) for these three SNPs had a poorer survival. Incorporating NUGs with clinical variables showed a significantly improved ability to classify CMSS (AUC increased from 86.8% to 88.6%, p = 0.031). Genetic variants in the integrin signaling pathway may independently or jointly modulate the survival of CM patients. Further large, prospective studies are needed to validate these findings.

Duke Scholars

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

March 15, 2017

Volume

140

Issue

6

Start / End Page

1270 / 1279

Location

United States

Related Subject Headings

  • rac GTP-Binding Proteins
  • p21-Activated Kinases
  • Young Adult
  • Skin Neoplasms
  • Signal Transduction
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Middle Aged
 

Citation

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Li, H., Wang, Y., Liu, H., Shi, Q., Xu, Y., Wu, W., … Wei, Q. (2017). Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival. Int J Cancer, 140(6), 1270–1279. https://doi.org/10.1002/ijc.30545
Li, Hongyu, Yanru Wang, Hongliang Liu, Qiong Shi, Yinghui Xu, Wenting Wu, Dakai Zhu, et al. “Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival.Int J Cancer 140, no. 6 (March 15, 2017): 1270–79. https://doi.org/10.1002/ijc.30545.
Li H, Wang Y, Liu H, Shi Q, Xu Y, Wu W, et al. Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival. Int J Cancer. 2017 Mar 15;140(6):1270–9.
Li, Hongyu, et al. “Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival.Int J Cancer, vol. 140, no. 6, Mar. 2017, pp. 1270–79. Pubmed, doi:10.1002/ijc.30545.
Li H, Wang Y, Liu H, Shi Q, Xu Y, Wu W, Zhu D, Amos CI, Fang S, Lee JE, Han J, Wei Q. Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival. Int J Cancer. 2017 Mar 15;140(6):1270–1279.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

March 15, 2017

Volume

140

Issue

6

Start / End Page

1270 / 1279

Location

United States

Related Subject Headings

  • rac GTP-Binding Proteins
  • p21-Activated Kinases
  • Young Adult
  • Skin Neoplasms
  • Signal Transduction
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Middle Aged