A genome-wide analysis of gene-caffeine consumption interaction on basal cell carcinoma.

Abstract

Animal models have suggested that oral or topical administration of caffeine could inhibit ultraviolet-induced carcinogenesis via the ataxia telangiectasia and rad3 (ATR)-related apoptosis. Previous epidemiological studies have demonstrated that increased caffeine consumption is associated with reduced risk of basal cell carcinoma (BCC). To identify common genetic markers that may modify this association, we tested gene-caffeine intake interaction on BCC risk in a genome-wide analysis. We included 3383 BCC cases and 8528 controls of European ancestry from the Nurses' Health Study and Health Professionals Follow-up Study. Single nucleotide polymorphism (SNP) rs142310826 near the NEIL3 gene showed a genome-wide significant interaction with caffeine consumption (P = 1.78 × 10-8 for interaction) on BCC risk. There was no gender difference for this interaction (P = 0.64 for heterogeneity). NEIL3, a gene belonging to the base excision DNA repair pathway, encodes a DNA glycosylase that recognizes and removes lesions produced by oxidative stress. In addition, we identified several loci with P value for interaction <5 × 10-7 in gender-specific analyses (P for heterogeneity between genders < 0.001) including those mapping to the genes LRRTM4, ATF3 and DCLRE1C in women and POTEA in men. Finally, we tested the associations between caffeine consumption-related SNPs reported by previous genome-wide association studies and risk of BCC, both individually and jointly, but found no significant association. In sum, we identified a DNA repair gene that could be involved in caffeine-mediated skin tumor inhibition. Further studies are warranted to confirm these findings.

• Authors: Xin Li, Marilyn C Cornelis, Liming Liang, Fengju Song, Immaculata De Vivo, Edward Giovannucci, Jean Y Tang, Jiali Han
• Journal: Carcinogenesis (Carcinogenesis) Vol. 37 Issue 12 Pg. 1138-1143 (Dec 2016) ISSN: 1460-2180 [Electronic] England
• PMID: 27797824 (Publication Type: Journal Article)
• Copyright: © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Caffeine
• ATR protein, human
• Ataxia Telangiectasia Mutated Proteins
• N-Glycosyl Hydrolases
• NEIL3 protein, human

Topics

• Animals
• Ataxia Telangiectasia Mutated Proteins (genetics)
• Caffeine (administration & dosage)
• Carcinogenesis (drug effects, genetics, radiation effects)
• Carcinoma, Basal Cell (chemically induced, drug therapy, genetics, pathology)
• Epistasis, Genetic (genetics)
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Male
• Mice
• N-Glycosyl Hydrolases (genetics)
• Polymorphism, Single Nucleotide
• Risk Factors
• Skin Neoplasms (chemically induced, drug therapy, genetics, pathology)
• Ultraviolet Rays (adverse effects)