Have questions? Visit https://www.reddit.com/r/SNPedia


From SNPedia

Geno Mag Summary
(A;A) 1.5 Faster caffeine metabolism in smokers and heavy coffee consumers
(A;C) 0 Carrier of one CYP1A2*1F allele; Normal metabolism of caffeine
(C;C) 0 Normal metabolism of caffeine.
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs762551
1000 genomesrs762551
GWAS Ctlgrs762551
Max Magnitude1.5
? (A;A) (A;C) (C;C) 28

rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. CYP1A2 is an enzyme responsible for the metabolism of caffeine and some drugs.

The baseline activity of the enzyme is similar in CYP1A2*1F allele carriers and non-carriers. However, rs762551(A) codes for the "high inducibility" form of the enzyme, characterized by higher enzyme activity in the presence of an inducer such as smoking or heavy coffee consumption [PMID 23167834]. In non-smokers, there was no significant difference in CYP1A2 activity between the genotypes. In smokers, however, the A/A homozygotes had 1.6x higher CYP1A2 activity than A/C and C/C genotypes [PMID 10233211OA-icon.png]. Similarly, among non-smokers, only in heavy coffee consumers (more than 3 cups daily) the A/A homozygotes had about 1.4x higher CYP1A2 activity. There was no differences in CYP1A2 activity by genotype in non-heavy coffee consumers. [PMID 20390257]

A study of healthy premenopausal non-hormone using women concluded that drinkers of 3 or more cups of coffee per day tended to have lower breast volume (smaller breasts), but only if they had at least one rs762551(C) allele (p(interaction)=0.02), which was said to be consistent with reports that coffee protects only C-allele carriers against breast cancer.[PMID 18813311OA-icon.png]

Another study by this same group looked at coffee consumption as related to breast cancer. Among 458 such patients (age 25-99 years), rs762551(A;A) women (about 1/2 of the total study) who drank 2 or more cups of coffee per day tended to have a later age at diagnosis compared with low coffee consumption (59.8 versus 52.6 years, p = 0.0004). These patients were also more likely to have ER- tumors than patients with low consumption (14.7% versus 0%, p = 0.018). Coffee consumption had no associations in carriers of a rs762551(C) allele.[PMID 18398030]

An independent study of 411 BRCA1 mutation carriers (170 cases and 241 controls) looked at the association between breast cancer, coffee consumption before age 35, and CYP1A2 genotype. While CYP1A2 genotype did not affect breast cancer risk, women with at least one rs762551(C) allele who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (odds ratio 0.36, CI: 0.18-0.73). No such protective effect was seen in rs762551(A;A) women.[PMID 17507615]

A study of 2,000 Costa Ricans who survived a first heart attack observed a general trend between coffee consumption and increased risk among carriers of rs762551(C) alleles, i.e. more coffee led to increased nonfatal heart attack risk. No association was seen for rs762551(A;A) individuals.[PMID 16522833]

[PMID 19415745] Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

[PMID 21281405OA-icon.png] Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease

[PMID 22492992] Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension.

[PMID 22648710] CYP1A2 and coffee intake and the modifying effect of sex, age, and smoking

[PMID 16172230] Risk of testicular germ cell cancer in relation to variation in maternal and offspring cytochrome p450 genes involved in catechol estrogen metabolism.

[PMID 17116718OA-icon.png] Dietary phytoestrogen intake is associated with reduced colorectal cancer risk.

[PMID 17160896OA-icon.png] Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants.

[PMID 17688403] Association of serotonin 2A receptor and lack of association of CYP1A2 gene polymorphism with tardive dyskinesia in a Turkish population.

[PMID 18075470] Association between caffeine intake and risk of Parkinson's disease among fast and slow metabolizers.

[PMID 18268115OA-icon.png] Meat intake, heterocyclic amine exposure, and metabolizing enzyme polymorphisms in relation to colorectal polyp risk.

[PMID 18632753OA-icon.png] Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes.

[PMID 18759349OA-icon.png] Coffee, caffeine-related genes, and Parkinson's disease: a case-control study.

[PMID 18798002OA-icon.png] Coffee consumption, genetic susceptibility and bladder cancer risk.

[PMID 18941913OA-icon.png] Coffee intake, variants in genes involved in caffeine metabolism, and the risk of epithelial ovarian cancer.

[PMID 18990750OA-icon.png] Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk.

[PMID 18992148OA-icon.png] Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.

[PMID 19287484OA-icon.png] Clique-finding for heterogeneity and multidimensionality in biomarker epidemiology research: the CHAMBER algorithm.

[PMID 19338043OA-icon.png] Genetic polymorphisms in glutathione S-transferases and cytochrome P450s, tobacco smoking, and risk of non-Hodgkin lymphoma.

[PMID 20304699OA-icon.png] Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson's disease in men and women.

[PMID 20389299OA-icon.png] Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.

[PMID 20559687] CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer.

[PMID 22466345OA-icon.png] Joint effects of smoking and gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women.

[PMID 23128882] Role of CYP1A2 polymorphisms in breast cancer risk in women

[PMID 23528250] Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women

[PMID 23530639] High Coffee Intake, but Not Caffeine, is Associated with Reduced Estrogen Receptor Negative and Postmenopausal Breast Cancer Risk with No Effect Modification by CYP1A2 Genotype

[PMID 23686565] Genetic polymorphism of cytochrome P450 (CYP) 1A1, CYP1A2, and CYP2E1 genes modulate susceptibility to gastric cancer in patients with Helicobacter pylori infection

[PMID 23130019OA-icon.png] Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.

[PMID 23157985OA-icon.png] CYP1A2 rs762551 polymorphism contributes to cancer susceptibility: a meta-analysis from 19 case-control studies.

[PMID 23175176OA-icon.png] Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype.

[PMID 23462460] Current evidence on the relationship between three polymorphisms in the CYP1A2 gene and the risk of cancer.

[PMID 23628800] Role of CYP1A2 1F polymorphism in cancer risk: evidence from a meta-analysis of 46 case-control studies.

[PMID 25081684] Four Polymorphisms in the Cytochrome P450 1A2 (CYP1A2) Gene and Lung Cancer Risk: a Meta-analysis

[PMID 26514519] Association between the CYP1A2 rs762551 Polymorphism and Bladder Cancer Susceptibility: a Meta-Analysis Based on Case-Control Studies

[PMID 29569539] Postprandial glycaemic and lipaemic responses to chronic coffee consumption may be modulated by CYP1A2 polymorphisms.

[PMID 30179617OA-icon.png] Coffee, Caffeine Metabolism Genotype, and Disease Progression in Localized Prostate Cancer Patients Managed with Active Surveillance.

[PMID 31477036OA-icon.png] Association of CYP gene polymorphisms with breast cancer risk and prognostic factors in the Jordanian population.

[PMID 32424513] CYP1A2 rs762551 and ADORA2A rs5760423 Polymorphisms in Patients with Blepharospasm.