title: 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 × 10-8for 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 × 10-7in 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: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA 02115, USA.
authors: Xin
authors: X
authors: Li
authors: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago IL 60611, USA.
authors: Marilyn C
authors: MC
authors: Cornelis
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA 02115, USA.
authors: Liming
authors: L
authors: Liang
authors: Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, Tianjin 300060, China.|National Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors: Fengju
authors: F
authors: Song
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA 02115, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Immaculata
authors: I
authors: De Vivo
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA 02115, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors: Edward
authors: E
authors: Giovannucci
authors: Department of Dermatology, Stanford University School of Medicine, Redwood City, CA 94063, USA.
authors: Jean Y
authors: JY
authors: Tang
authors: Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN 46202, USA jialhan@iu.edu.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA.|Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN 46202, USA.
authors: Jiali
authors: J
authors: Han
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D002110:Caffeine / Q000008:administration & dosage*; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002280:Basal Cell Carcinoma / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D002110:Caffeine; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D009699:N-Glycosyl Hydrolases; C468764:NEIL3 protein, human