rs762551

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 . 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 . 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. 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. 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. 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. 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.

A;A

Highly inducible form of CYP1A2 enzyme. 1.6x faster caffeine metabolism in smokers. 1.4x faster caffeine metabolism in heavy coffee consumers (more than 3 cups).