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.

Acute effects of coffee on skin blood flow and microvascular function

“…Most studies find that regular coffee intake increases blood pressure slightly and raises plasma cholesterol and homocysteine levels [1], whereas coffee consumption is associated with a reduced incidence of type 2 diabetes mellitus [2], a decrease in inflammatory markers [3] and improved endothelial function [4]. Caffeine consumption also affects pain modulation [5] and interacts with skin carcinomas, with some evidence pointing at a protective effect of caffeine on malignant melanoma [6,7].…”

Caffeine Inhibits Growth of Temozolomide-Treated Glioma via Increasing Autophagy and Apoptosis but Not via Modulating Hypoxia, Angiogenesis, or Endoplasmic Reticulum Stress in Rats

“…Fluoxetine synergizes with TMZ to induce the CHOP-dependent ER stress-related apoptosis pathway in glioma cells (20). As for caffeine, it could inhibit ultraviolet-induced skin carcinogenesis via increasing a DNA repair gene (NEIL3) expression and increasing the ataxia telangiectasia and rad3 (ATR)-related apoptosis (21). Caffeine could induce premature chromosome condensation and result in cell death in root meristems of Vicia faba (22).…”

DGAT-onco: A differential analysis method to detect oncogenes by integrating functional information of mutations

“…Literature reviews showed that 14 genes have were related with cancers (Ahn, et al, 2019;Chiou, et al, 2019;Ishiuchi, et al, 2002;Li, et al, 2019;Li, et al, 2016;Li, et al, 2017;Liu, et al, 2019;Malik, et al, 2019;Michiels, et al, 2007;Oakes, et al, 2017;Wang, et al, 2019;Yao, et al, 2018;Yu, et al, 2015). Among these genes, KRAS, NRAS and TP53 are common oncogenes in cancer studies, while CDH10, GABRG2, GRIA2, KCNK9, SOX5, ERCC5, HIST1H4H, LRRTM4 were recently verified as cancer-related gene by wet-lab experiments.…”