title: Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Epidemiology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Kirsten A M
authors.initials: KA
authors.lastname: White
authors.affiliation: Department of Medicine, Division of Epidemiology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Thompson
authors.affiliation: Center for HPV Prevention, Department of Pathology University of New Mexico, Albuquerque, New Mexico.
authors.forename: Salina
authors.initials: S
authors.lastname: Torres
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Chien-An Andy
authors.initials: CA
authors.lastname: Hu
authors.affiliation: Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Division of Epidemiology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Jenna
authors.initials: J
authors.lastname: Lilyquist
authors.affiliation: Department of Epidemiology, School of Medicine, University of California, Irvine, California.
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.affiliation: Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.affiliation: Cancer Care Ontario, Toronto, Ontario, Canada.
authors.forename: Lynn
authors.initials: L
authors.lastname: From
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.affiliation: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.affiliation: Cancer Care Ontario, Toronto, Ontario, Canada.
authors.forename: Loraine D
authors.initials: LD
authors.lastname: Marrett
authors.affiliation: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Gallagher
authors.affiliation: Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sacchetto
authors.affiliation: Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosso
authors.affiliation: George Institute for Global Health, University of Oxford, UK.
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
authors.affiliation: University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cust
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.affiliation: Department of Medicine, Division of Epidemiology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D008954:Models, Biological; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins
keywords: 
  ATG16L1
  ; 
  SNP
  ; autophagy; melanoma; polymorphism