TY - JOUR AU - Kanetsky P. AU - Dwyer T AU - Orlow I. AU - Luo L. AU - Anton-Culver H. AU - Gruber S. AU - Marrett L. AU - Gallagher R. AU - Rosso S. AU - From L. AU - Busam K. AU - Cust A. AU - Begg C. AU - Berwick M. AU - Thomas N. AU - White K. AU - Thompson T. AU - Torres S. AU - Hu C. AU - Lilyquist J. AU - Sacchetto L. AB -

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.

AD - Department of Medicine, Division of Epidemiology, University of New Mexico, Albuquerque, New Mexico.
Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico.
Center for HPV Prevention, Department of Pathology University of New Mexico, Albuquerque, New Mexico.
Department of Biochemistry and Molecular Biology, University of New Mexico, Albuquerque, New Mexico.
Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
Department of Epidemiology, School of Medicine, University of California, Irvine, California.
Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Cancer Care Ontario, Toronto, Ontario, Canada.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Turin, Italy.
George Institute for Global Health, University of Oxford, UK.
University of Sydney, Sydney, New South Wales, Australia.
Department of Medicine, Division of Epidemiology, University of New Mexico, Albuquerque, New Mexico. mberwick@salud.unm.edu. AN - 27748080 BT - Cancer Med CN - [IF]: 2.915 DP - NLM ET - 2016/10/18 J2 - Cancer medicine LA - Eng LB - UK
FY17 M1 - 11 N1 - White, Kirsten A M
Luo, Li
Thompson, Todd A
Torres, Salina
Hu, Chien-An Andy
Thomas, Nancy E
Lilyquist, Jenna
Anton-Culver, Hoda
Gruber, Stephen B
From, Lynn
Busam, Klaus J
Orlow, Irene
Kanetsky, Peter A
Marrett, Loraine D
Gallagher, Richard P
Sacchetto, Lidia
Rosso, Stefano
Dwyer, Terence
Cust, Anne E
Begg, Colin B
Berwick, Marianne
GEM Study Group
United States
Cancer Med. 2016 Oct 17. doi: 10.1002/cam4.929. N2 -

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.

PY - 2016 SN - 2045-7634 (Electronic)
2045-7634 (Linking) SP - 3336 EP - 45 ST - Cancer medicineCancer medicine T2 - Cancer Med TI - Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study VL - 5 Y2 - FY17 ER -