Skip to main content
Journal cover image

Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.

Publication ,  Journal Article
Dai, W; Liu, H; Liu, Y; Xu, X; Qian, D; Luo, S; Cho, E; Zhu, D; Amos, CI; Fang, S; Lee, JE; Li, X; Nan, H; Li, C; Wei, Q
Published in: Br J Dermatol
October 2020

BACKGROUND: Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWASs) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. OBJECTIVES: To examine associations between SNPs in folate metabolic pathway genes and CMSS. METHODS: We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively. RESULTS: We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32-2·32, P = 9·96 × 10-5 ) and 2·05 (1·39-3·01, P = 2·84 × 10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. CONCLUSIONS: Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic? Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma-specific prognosis. A hypothesis-driven approach, by pooling the effects of single-nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add? Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma-specific survival (CMSS). What is the translational message? The identification of genetic variants will make a risk-prediction model possible for CMSS. The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Br J Dermatol

DOI

EISSN

1365-2133

Publication Date

October 2020

Volume

183

Issue

4

Start / End Page

719 / 728

Location

England

Related Subject Headings

  • Skin Neoplasms
  • Polymorphism, Single Nucleotide
  • Metabolic Networks and Pathways
  • Melanoma
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Follow-Up Studies
  • Folic Acid
  • Dermatology & Venereal Diseases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dai, W., Liu, H., Liu, Y., Xu, X., Qian, D., Luo, S., … Wei, Q. (2020). Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival. Br J Dermatol, 183(4), 719–728. https://doi.org/10.1111/bjd.18878
Dai, W., H. Liu, Y. Liu, X. Xu, D. Qian, S. Luo, E. Cho, et al. “Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.Br J Dermatol 183, no. 4 (October 2020): 719–28. https://doi.org/10.1111/bjd.18878.
Dai W, Liu H, Liu Y, Xu X, Qian D, Luo S, et al. Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival. Br J Dermatol. 2020 Oct;183(4):719–28.
Dai, W., et al. “Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.Br J Dermatol, vol. 183, no. 4, Oct. 2020, pp. 719–28. Pubmed, doi:10.1111/bjd.18878.
Dai W, Liu H, Liu Y, Xu X, Qian D, Luo S, Cho E, Zhu D, Amos CI, Fang S, Lee JE, Li X, Nan H, Li C, Wei Q. Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival. Br J Dermatol. 2020 Oct;183(4):719–728.
Journal cover image

Published In

Br J Dermatol

DOI

EISSN

1365-2133

Publication Date

October 2020

Volume

183

Issue

4

Start / End Page

719 / 728

Location

England

Related Subject Headings

  • Skin Neoplasms
  • Polymorphism, Single Nucleotide
  • Metabolic Networks and Pathways
  • Melanoma
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Follow-Up Studies
  • Folic Acid
  • Dermatology & Venereal Diseases