Disease-associated risk variants in ANRIL are associated with tumor-infiltrating lymphocyte presence in primary melanomas in the population-based GEM study Journal Article


Authors: Davari, D. R.; Orlow, I.; Kanetsky, P. A.; Luo, L.; Edmiston, S. N.; Conway, K.; Parrish, E. A.; Hao, H.; Busam, K. J.; Sharma, A.; Kricker, A.; Cust, A. E.; Ahton-Culver, H.; Gruber, S. B.; Gallagher, R. P.; Zabetti, R.; Rosso, S.; Sacchetto, L.; Dwyer, T.; Ollita, D. W.; Begg, C. B.; Berwick, M.; Thomas, N. E.; on behalf of the GEM Study Group
Contributors: Orlow, I.; Busam, K. J.; Autuori, I.; Mauguen, A.; Roy, P.; Yoo, S.; Sharma, A.; Rayar, J.
Article Title: Disease-associated risk variants in ANRIL are associated with tumor-infiltrating lymphocyte presence in primary melanomas in the population-based GEM study
Abstract: Background: Genome-wide association studies have reported that genetic variation at ANRIL (CDKN2B-AS1) is associated with risk of several chronic diseases including coronary artery disease, coronary artery calcification, myocardial infarction, and type 2 diabetes mellitus. ANRIL is located at the CDKN2A/B locus, which encodes multiple melanoma tumor suppressors. We investigated the association of these variants with melanoma prognostic characteristics. Methods: The Genes, Environment, and Melanoma Study enrolled 3,285 European origin participants with incident invasive primary melanoma. For each of ten disease-associated SNPs at or near ANRIL, we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and ORs for presence of ulceration and tumor-infiltrating lymphocytes (TIL). We also assessed effect modification by tumor NRAS/ BRAF mutational status. Results: Rs518394, rs10965215, and rs564398 passed false discovery and were each associated (P <= 0.005) with TILs, although only rs564398 was independently associated (P = 0.0005) with TILs. Stratified by NRAS/BRAF mutational status, rs564398*A was significantly positively associated with TILs among NRAS/BRAF mutant, but not wild-type, cases. We did not find SNP associations with Breslow thickness or ulceration. Conclusions: ANRIL rs564398 was associated with TIL presence in primary melanomas, and this association may be limited to NRAS/BRAF-mutant cases. Impact: Pathways related to ANRIL variants warrant exploration in relationship to TILs in melanoma, especially given the impact of TILs on immunotherapy and survival.
Keywords: survival; atherosclerosis; coronary artery disease; malignant-melanoma; clinicopathological features; environment; polymorphisms; locus; genetic-variants; myocardial; incident; coronary artery calci fi cation; noncoding rna anril
Journal Title: Cancer Epidemiology Biomarkers and Prevention
Volume: 30
Issue: 12
ISSN: 1055-9965
Publisher: American Association for Cancer Research  
Date Published: 2021-12-01
Start Page: 2309
End Page: 2316
Language: English
ACCESSION: WOS:000728334200001
DOI: 10.1158/1055-9965.Epi-21-0686
PROVIDER: wos
PMCID: PMC8643342
PUBMED: 34607836
Notes: Article -- Source: Wos
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MSK Authors
  1. Colin B Begg
    306 Begg
  2. Irene Orlow
    247 Orlow
  3. Klaus J Busam
    690 Busam
  4. Pampa Roy
    36 Roy
  5. Ajay P Sharma
    13 Sharma
  6. Audrey   Mauguen
    157 Mauguen
  7. Sarah Min Kyung Yoo
    20 Yoo