Format

Send to

Choose Destination
Int J Cancer. 2017 Mar 15;140(6):1270-1279. doi: 10.1002/ijc.30545. Epub 2016 Dec 19.

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

Li H1,2,3, Wang Y1,2, Liu H1,2, Shi Q1,2,4, Xu Y1,2,5, Wu W6, Zhu D7, Amos CI7, Fang S8, Lee JE8, Han J6,9, Wei Q1,2.

Author information

1
Duke Cancer Institute, Duke University Medical Center, Durham, NC.
2
Department of Medicine, Duke University School of Medicine, Durham, NC.
3
Department of Gastroenterology, Shenyang Northern Hospital, Shenyang, Liaoning, 110840, China.
4
Department of Dermatology, Xijing Hospital, Xi'an, Shanxi, 710032, China.
5
Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
6
Department of Epidemiology, Fairbanks School of Public Health, Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
7
Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH.
8
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX.
9
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.

Abstract

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.

KEYWORDS:

cutaneous melanoma; cutaneous melanoma-specific survival; genome-wide association study; integrin signaling pathway; single-nucleotide polymorphism

PMID:
27914105
PMCID:
PMC5272783
DOI:
10.1002/ijc.30545
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center