It has been more than 150 years since Gregor Mendel reported inheritance factors in pea plants. Approximately 15 years ago, the Human Genome Project was completed. These observations and advances in understanding inheritance factors, now known as DNA, have sparked innovations in nutrition, medicine, and agriculture. More recently, DNA testing, which purportedly provides consumers with information regarding their DNA relative to their heritage and health, has become increasingly popular. Consumers can now educate themselves on certain single-nucleotide polymorphisms (SNP) and the respective variations within their unique human genome.

SNPs can be thought of as discrete families of DNA building blocks, markers, or hot spots that occur at regular intervals of about 300 nucleotides. Depending on their composition and where they occur within a coding sequence, certain rapid associations or conclusions about what is being encoded can be determined.

Cytochrome P450 (CYP) represents one such family of genes. These genes are involved in the formation (synthesis) and breakdown (metabolism) of various substances. For example, dietary substances such as caffeine, theophylline, and theobromine, which are components of coffee, tea, and cocoa, are metabolized by this cluster of genes. Specifically, gene CYP1A2 within the CYP cluster is found with CYP1A1 and CYP1B1 on chromosome 15 (Kalow and Tang 1993).

Caffeine is almost 100% metabolized by most humans; < 3% is excreted in urine. Importantly, caffeine is metabolized by CYP1A2 in the liver. Rs762551 is the allele that encodes the CYP1A2*1F allele of the CYP1A2 gene. If you are a homozygous carrier of the C allele (C:C), you are a slow caffeine metabolizer (Denden et al. 2016). There are several other variants of SNP, such as 7p21 and 15q24, that also affect caffeine metabolism (Cornelis et al. 2016).

More than half of the U.S. adult population, or about 150 million people, drink espresso, cappuccino, latte, or iced/cold coffees. An individual’s genetics affect how quickly caffeine from these products is metabolized and how much one is able to consume. If you are a fast caffeine metabolizer, current research shows there is a link with a decreased risk of heart attack (Chrysant 2017). There are also links showing caffeine, when consumed in the form of 4–5 cups of coffee daily, may be effective at reducing the risk of some forms of breast cancer, Alzheimer’s disease, and Parkinson’s disease (Rosendahl et al. 2015, Oñatibia-Astibia et al. 2016).

Parkinson’s Disease. Caffeine may provide protective effects relative to Parkinson’s disease and other neurodegenerative disease (Chuang et al. 2016, Oñatibia-Astibia et al. 2016). The prevalence of this age-related neurodegenerative disorder varies from 100 to 250 per 100,000 population in North America and Europe.

Caffeine functions as an adenosine receptor antagonist. Coffee, with specific attention given to caffeine intake, is an environmental factor that has been associated with Parkinson’s disease in many studies, yet not all studies have demonstrated this association. Several studies indicate that the protective effects of coffee/caffeine intake are gender specific. Estrogen status plays a factor, suggesting more of protective factor in men (Yamada-Fowler and Söderkvist 2015).

A study among 446 sibling pairs and 158 unrelated pairs concluded that SNP CYP1A2 showed no association with the risk of Parkinson’s disease (Facheris et al. 2008). Furthermore, another study among 1,325 cases of Parkinson’s disease indicated two ADORA2A polymorphisms were weakly inversely associated with the disease, yet slow metabolizers who were homozygous carriers of the CYP1A2 polymorphisms reduced the risk of Parkinson’s disease (Popat et al. 2011). As one would expect, additional studies are needed to further evaluate the association of CYP1A2 and Parkinson’s disease. Meanwhile, results should be interpreted with caution (Elbers et al. 2015).

Breast Cancer. Coffee consumption and susceptibility to breast cancer may be related to two genes: BRCA1 or BRCA2. In addition to the presence of these genes, the impact of coffee consumption and some forms of breast cancer depends on whether the person is estrogen receptor positive or negative (Li et al. 2011). Mutations of BRCA genes among women who consume six or more cups of caffeinated coffee daily versus those who do not consume coffee were studied by Nkondjock et al. (2006). BRCA1 had a higher association than BRCA2. A decade ago, a study among 170 women with breast cancer and 241 controls indicated CYP1A2 genotype modifies breast cancer risk (Kotsopoulos et al. 2007). Women who had one variant C allele (AC or CC) and consumed coffee before the age of 35 had a 64% reduction in breast cancer risk compared with non-coffee drinkers. There is no significant impact with CYP1A2 AA genotypes.

Myocardial Infarction. A longitudinal study conducted in Costa Rica among 2,014 individuals who experienced a first acute nonfatal myocardial infarction (MI) concluded that coffee consumption increased MI risk only among slow caffeine metabolizers (Kabagambe et al. 2007). This study noted that regardless of whether one is a slow or fast caffeine metabolizer, factors such as age, smoking, and diet choices can modify this metabolic effect. A study among 100 Serbian and 149 Swedish healthy volunteers evaluated the potential coffee-influenced CYP1A2 enzyme activity (Djordjevic et al. 2008). This study indicated 3 or more cups of coffee daily resulted in increased CYP1A2 enzyme activity. In general, these and similar studies suggest that regardless of whether a person is a fast or slow metabolizer, heart disease can be influenced by other factors, such as sex, age, smoking versus non-smoking, the amount and type of coffee consumed, and physical activity (Rodenberg et al. 2015).

The evidence that suggests coffee consumption may reduce the risk of developing Parkinson’s disease, some forms of breast cancer, or heart disease is inconsistent. This effect is impacted by several variables, including specific genes and SNP and the volume of coffee consumption. Additional research is required, with greater attention among specific SNP variants and the consumption of methylxanthine-containing beverages. The preponderance of evidence indicates lifestyle habits may play a role in contributing to the risk of heart disease, Parkinson’s disease, and various forms of breast cancer in some individuals or within some populations. What may be more important about the “caffeine genes” is that they serve as a powerful tool that may allow us to rapidly identify or unravel clusters of genes that may represent vulnerability or resistance to pathology.


Roger ClemensRoger Clemens, DrPH, CFS,
Contributing Editor
Adjunct Professor,
Univ. of Southern California School of Pharmacy,
Los Angeles, Calif.
[email protected]

Sarah Khan is a master’s degree candidate at the Univ. of Southern California Leonard Davis School of Gerontology ([email protected]).