Know any genomes at Twitter support? Contact us if you can help get their attention.
rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. For historic reasons, the rs762551(C) allele is considered the wild-type, even though it is the rarer allele in most populations. The rs762551(A) allele is the "fast metabolizer" allele known as CYP1A2*1F; the (C) allele is by comparison a slower metabolizer of certain substrates (including caffeine).
In terms of genotypes, only rs762551(A;A) individuals are considered fast metabolizers. Individuals who are rs762551(A;C) heterozygotes or rs762551(C;C) homozygotes are both considered slow metabolizers.
The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. One well known substrate of CYP1A2 is caffeine; individuals who are carry one or more CYP1A2*1C alleles are "slow" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "fast" caffeine metabolizers. The same amount of caffeine will therefore tend to have more stimulating effect on CYP1A2 slow metabolizers than on CYP1A2 fast metabolizers.
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 18813311]
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 21281405] 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 17116718] Dietary phytoestrogen intake is associated with reduced colorectal cancer risk.
[PMID 17160896] 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 18268115] Meat intake, heterocyclic amine exposure, and metabolizing enzyme polymorphisms in relation to colorectal polyp risk.
[PMID 18632753] Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes.
[PMID 18759349] Coffee, caffeine-related genes, and Parkinson's disease: a case-control study.
[PMID 18798002] Coffee consumption, genetic susceptibility and bladder cancer risk.
[PMID 18941913] Coffee intake, variants in genes involved in caffeine metabolism, and the risk of epithelial ovarian cancer.
[PMID 18990750] Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk.
[PMID 18992148] Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.
[PMID 19287484] Clique-finding for heterogeneity and multidimensionality in biomarker epidemiology research: the CHAMBER algorithm.
[PMID 19338043] Genetic polymorphisms in glutathione S-transferases and cytochrome P450s, tobacco smoking, and risk of non-Hodgkin lymphoma.
[PMID 20304699] Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson's disease in men and women.
[PMID 20389299] 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 22466345] Joint effects of smoking and gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women.
|qualified_impact||Insufficiently evaluated pharmacogenetic|
[PMID 23128882] Role of CYP1A2 polymorphisms in breast cancer risk in women
[PMID 23492908] Influence of CYP1A1/CYP1A2 and AHR polymorphisms on systemic olanzapine exposure
[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 23130019] Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.
[PMID 23157985] CYP1A2 rs762551 polymorphism contributes to cancer susceptibility: a meta-analysis from 19 case-control studies.
[PMID 23175176] 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.