Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.

Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE

Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-

Genetic Predisposition to Disease* ; Genetic Variation* ; Population Surveillance*; Autophagy/*genetics ; Melanoma/*epidemiology ; Melanoma/*genetics; Adult ; Aged ; Alleles ; Autophagy-Related Proteins/genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Models, Biological ; Neoplasm Staging ; Odds Ratio ; Polymorphism, Single Nucleotide

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.
(© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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P30 ES010126 United States ES NIEHS NIH HHS; R25 CA092049 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R01 CA112243 United States CA NCI NIH HHS; K12 GM088021 United States GM NIGMS NIH HHS

Investigator: U Mujumdar; P Roy; B Armstrong; A Kricker; M Litchfield; P Tucker; A Venn; N Stephens; T Switzer; L Marrett; E Theis; N Chowdhury; L Vanasse; R Zanetti; C Sacerdote; N Leighton; J Jeter; J Klotz; H Wilcox; H Weiss; D Mattingly; J Player; T Rebbeck; A Walker; S Panossian; JL Taylor; S Madronich
Keywords: ATG16L1; SNP; autophagy; melanoma; polymorphism

0 (ATG16L1 protein, human)
0 (Autophagy-Related Proteins)

Date Created: 20161018 Date Completed: 20171116 Latest Revision: 20210109

20221213

PMC5119988

10.1002/cam4.929

27748080