|(A;A)||2||Fast Caffeine Metabolizer.|
|(A;C)||2.1||Carrier of one CYP1A2*1F allele; Slow Caffeine Metabolizer.|
|(C;C)||2.5||CYP1A2 slow caffeine metabolizer.|
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]
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[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.
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[PMID 18759349] Coffee, caffeine-related genes, and Parkinson's disease: a case-control study.
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[PMID 18992148] Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.
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|qualified_impact||Insufficiently evaluated pharmacogenetic|
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