Rs762551

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.