Coffee and Cancer: A More Complicated Story Than You Think

Of all the beverages studied for cancer associations, coffee generates some of the most consistently protective signals and some of the most context-dependent risks. The global evidence is now substantial enough that it deserves more than a summary dismissal or uncritical celebration. Coffee acts on multiple biological pathways at the same time, and whether that activity increases or reduces cancer risk depends on the type of cancer, a person’s genetic background, how much they drink, and how it is prepared.

The Case for Protection

The strongest and most consistent evidence that coffee may help reduce cancer risk comes from studies of liver and endometrial cancers, where the World Cancer Research Fund classifies the protective link as probable. For colorectal cancer, the evidence is more limited and should be seen as suggestive rather than firmly established. A 2024 comprehensive review by Kunutsor et al. in GeroScience pulled together data from multiple large studies and found that people who drink coffee regularly tend to have lower rates of hepatocellular carcinoma (HCC, the most common form of liver cancer), endometrial cancer, oral cancer, and colorectal cancer, with a pattern suggesting that drinking more coffee may offer greater protection up to a point [1]. A landmark umbrella review by Poole et al. (2017) in the BMJ, covering 201 sets of observational evidence, found that coffee was more often associated with health benefit than harm, including lower cancer rates, though the authors were clear that randomised trial evidence is still needed before firm causal conclusions can be drawn [2].

For liver cancer specifically, the biological case is compelling. Coffee reduces circulating levels of liver enzymes (ALT, AST), slows the build-up of liver scarring, and alters bile acid metabolism. Caffeine also blocks adenosine receptors on liver-resident cells called stellate cells, reducing the tissue damage and fibrosis that can eventually progress to cirrhosis and liver cancer [1, 2].

Cai et al. (2024) used a method called Mendelian randomisation (MR), which uses inherited genetic variants to estimate causal effects rather than relying on observed behaviour alone, to test the coffee-liver cancer link in East Asian populations. Their analysis found that people with genetic variants associated with higher coffee consumption also tended to have lower liver cancer risk. However, when the researchers removed one specific genetic variant (rs671, in a gene called ALDH2), the protective signal disappeared [3]. This means the evidence from this study should be read as promising but not yet conclusive, and any MR finding depends heavily on whether the genetic instruments used are truly valid.

The Molecular Mechanisms

Coffee is not a single compound. It contains hundreds to more than 1,000 chemical constituents, including several well-studied bioactive molecules: chlorogenic acids, two diterpenes called cafestol and kahweol, trigonelline, caffeine itself, and roasting-derived compounds called melanoidins [4]. Its potential anticancer effects come from several of these working simultaneously:

• Antioxidant activity: Chlorogenic acids are the main polyphenols in coffee and are effective at neutralising the free radicals that can damage DNA. Research compiled by Ludwig et al. found that coffee constituents, including chlorogenic acids and compounds produced during roasting, can activate the body’s own antioxidant defence systems and have been shown to reduce DNA damage in laboratory models [4].
• Anti-inflammatory effects: Regular coffee drinking has been linked to lower levels of inflammation markers in the blood. A randomised controlled trial by Kempf et al. (2010) found that people who drank filtered coffee showed improved inflammation profiles and metabolic markers compared to those who abstained, over a four-week period [5].
• Metabolic effects: Coffee drinking is linked to a lower risk of developing type 2 diabetes. A systematic review by van Dam and Hu (2005) in JAMA found that people who drank coffee regularly were less likely to develop type 2 diabetes across multiple independent studies [6]. This matters for cancer because high insulin levels and elevated IGF-1, both features of poor metabolic health, can fuel tumour growth in several organs, particularly the colon, endometrium, and pancreas. Coffee’s metabolic benefits may therefore contribute to some of its cancer-risk signals.
• DNA repair support: Cafestol and kahweol, alongside chlorogenic acids, have been shown to boost DNA repair activity and increase the production of enzymes that help the body detoxify carcinogens before they cause lasting DNA damage [4].

Where the Risk Signals Appear

Not all the findings point in a protective direction. Kunutsor et al. (2024) also found a link between coffee drinking and higher lung cancer rates, though this is one of the most heavily confounded associations in the field. Historically, coffee drinking and cigarette smoking have gone hand in hand in many populations, making it genuinely difficult to separate their effects [1]. The lung cancer signal in coffee research should be read with that caveat front of mind.

The International Agency for Research on Cancer (IARC), following their evaluation published in IARC Monograph Volume 116, classified very hot beverages drunk above 65°C as Group 2A (probably carcinogenic to humans), linked mainly to heat damage to the lining of the throat and oesophagus [7]. It is important to be clear: coffee itself was classified as Group 3, meaning it could not be classified as carcinogenic. The risk IARC identified is about drinking any liquid at very high temperatures, not about coffee’s chemistry.

Genetic Variation in Caffeine Metabolism

The liver enzyme CYP1A2 is mainly responsible for breaking down caffeine. Common gene variants in CYP1A2 produce fast and slow metaboliser types, which change how long caffeine stays in the body and affect the levels of other coffee compounds that reach tissues. A study by Cornelis et al. (2006) in JAMA showed that whether coffee raised or lowered cardiovascular risk depended on which version of this gene a person carried, a clear example of how the same dietary behaviour can have different effects in different people [8]. This principle likely extends to cancer pharmacology as well, though the data at the cancer-specific level are not yet robust enough for firm conclusions.

What This Means in Practice

For most adults, drinking coffee in moderate amounts, roughly 3 to 4 cups per day, is associated with lower cancer risk when liver and endometrial cancer data are considered, though effect sizes vary across studies and cancer types [1, 2]. The evidence does not support the idea that coffee is a broadly dangerous drink. What it does support is the view that how coffee is consumed shapes what it actually does to cancer risk in any given individual: its temperature, the genetic background of the person drinking it, and what other risk factors are present all matter. One-size-fits-all recommendations, in either direction, miss most of the complexity.

Bibliography

1. Kunutsor SK, Lehoczki A and Laukkanen JA (2024) Coffee consumption, cancer, and healthy aging: epidemiological evidence and underlying mechanisms. GeroScience 47:1517–1555.
2. Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC and Parkes J (2017) Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ 359:j5024.
3. Cai H, Xu X, Zhang T, Tian T and Wang Y (2024) The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis. Sci Rep 14:9682.
4. Ludwig IA, Clifford MN, Lean MEJ, Ashihara H and Crozier A (2014) Coffee: biochemistry and potential impact on health. Food Funct 5:1695–1717.
5. Kempf K, Herder C, Erlund I, Kolb H, Martin S, Carstensen M, Koenig W, Sundvall J, Bidel S, Kuha S and Tuomilehto J (2010) Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr 91:950–957.
6. van Dam RM and Hu FB (2005) Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 294:97–104.
7. Loomis D, Guyton KZ, Grosse Y, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Mattock H, Straif K and International Agency for Research on Cancer Monograph Working Group (2016) Carcinogenicity of drinking coffee, mate, and very hot beverages. Lancet Oncol 17:877–878.
8. Cornelis MC, El-Sohemy A, Kabagambe EK and Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–1141.