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Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk.

Publication ,  Journal Article
Liu, H; Wang, L-E; Liu, Z; Chen, WV; Amos, CI; Lee, JE; Q-MEGA and AMFS Investigators, ; GenoMEL Investigators, ; Iles, MM; Law, MH; Taylor, JC ...
Published in: Carcinogenesis
April 2013

Genome-wide association studies (GWASs) have mainly focused on top significant single nucleotide polymorphisms (SNPs), most of which did not have clear biological functions but were just surrogates for unknown causal variants. Studying SNPs with modest association and putative functions in biologically plausible pathways has become one complementary approach to GWASs. To unravel the key roles of mitogen-activated protein kinase (MAPK) pathways in cutaneous melanoma (CM) risk, we re-evaluated the associations between 47 818 SNPs in 280 MAPK genes and CM risk using our published GWAS dataset with 1804 CM cases and 1026 controls. We initially found 105 SNPs with P ≤ 0.001, more than expected by chance, 26 of which were predicted to be putatively functional SNPs. The risk associations with 16 SNPs around DUSP14 (rs1051849) and a previous reported melanoma locus MAFF/PLA2G6 (proxy SNP rs4608623) were replicated in the GenoMEL dataset (P < 0.01) but failed in the Australian dataset. Meta-analysis showed that rs1051849 in the 3' untranslated regions of DUSP14 was associated with a reduced risk of melanoma (odds ratio = 0.89, 95% confidence interval: 0.82-0.96, P = 0.003, false discovery rate = 0.056). Further genotype-phenotype correlation analysis using the 90 HapMap lymphoblastoid cell lines from Caucasians showed significant correlations between two SNPs (rs1051849 and rs4608623) and messenger RNA expression levels of DUSP14 and MAFF (P = 0.025 and P = 0.010, respectively). Gene-based tests also revealed significant SNPs were over-represented in MAFF, PLA2G6, DUSP14 and other 16 genes. Our results suggest that functional SNPs in MAPK pathways may contribute to CM risk. Further studies are warranted to validate our findings.

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Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2013

Volume

34

Issue

4

Start / End Page

885 / 892

Location

England

Related Subject Headings

  • Skin Neoplasms
  • Skin
  • Risk
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Phosphatases
  • Middle Aged
 

Citation

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Liu, H., Wang, L.-E., Liu, Z., Chen, W. V., Amos, C. I., Lee, J. E., … Wei, Q. (2013). Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk. Carcinogenesis, 34(4), 885–892. https://doi.org/10.1093/carcin/bgs407
Liu, Hongliang, Li-E Wang, Zhensheng Liu, Wei V. Chen, Christopher I. Amos, Jeffrey E. Lee, Jeffrey E. Q-MEGA and AMFS Investigators, et al. “Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk.Carcinogenesis 34, no. 4 (April 2013): 885–92. https://doi.org/10.1093/carcin/bgs407.
Liu H, Wang L-E, Liu Z, Chen WV, Amos CI, Lee JE, et al. Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk. Carcinogenesis. 2013 Apr;34(4):885–92.
Liu, Hongliang, et al. “Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk.Carcinogenesis, vol. 34, no. 4, Apr. 2013, pp. 885–92. Pubmed, doi:10.1093/carcin/bgs407.
Liu H, Wang L-E, Liu Z, Chen WV, Amos CI, Lee JE, Q-MEGA and AMFS Investigators, GenoMEL Investigators, Iles MM, Law MH, Barrett JH, Montgomery GW, Taylor JC, MacGregor S, Cust AE, Newton Bishop JA, Hayward NK, Bishop DT, Mann GJ, Affleck P, Wei Q. Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk. Carcinogenesis. 2013 Apr;34(4):885–892.

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2013

Volume

34

Issue

4

Start / End Page

885 / 892

Location

England

Related Subject Headings

  • Skin Neoplasms
  • Skin
  • Risk
  • RNA, Messenger
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Phosphatases
  • Middle Aged