What Drugs and Medications Increase Your Cancer Risk?

Dozens of prescription and over-the-counter medications carry some documented association with cancer, though the size of that risk varies enormously depending on the drug, the dose, and how long you take it. The list ranges from powerful immunosuppressants that can multiply cancer risk several-fold to common heartburn pills where the link is still debated. Understanding which drugs have the strongest evidence behind them, and what kind of cancer they’re connected to, can help you have more informed conversations with your doctor about the tradeoffs of any long-term medication.

Immunosuppressants After Organ Transplant

If there is one drug category with the most dramatic and well-documented cancer risk, it is the immunosuppressive medications given to organ transplant recipients. These drugs keep your immune system from attacking the new organ, but that same suppression weakens your body’s ability to detect and destroy abnormal cells before they become tumors. Studies and cancer registries have consistently shown elevated malignancy rates in transplant patients, with risk increases reported anywhere from four-fold to 500-fold depending on the cancer type and study methodology.

Skin cancer is by far the most common malignancy in transplant recipients, accounting for over half of post-transplant cancers in one large multicenter analysis. Lymphomas and Kaposi’s sarcoma are also sharply overrepresented. Among specific drugs, azathioprine carried the highest hazard in that study, roughly doubling the risk of post-transplant cancer, while cyclosporine raised it by about 60%. Interestingly, tacrolimus was associated with lower cancer rates in the same analysis, suggesting that the choice of immunosuppressive regimen matters.

A nationwide Korean cohort study looking at drugs classified as Group 1 carcinogens by the International Agency for Research on Cancer put numbers on several of these. Azathioprine users had roughly 4.6 times the risk of skin cancer and about three times the risk of blood cancers. Cyclosporine users showed elevated risk for both skin and blood cancers as well. Cyclophosphamide, an immunosuppressant also used in chemotherapy, was linked to nearly 2.7 times the risk of bladder cancer and close to four times the risk of blood cancers. Melphalan, another alkylating agent, stood out with over 16 times the risk of hematologic malignancy.

None of this means transplant recipients should stop their medications. Organ rejection is a far more immediate threat than a possible future cancer. But these numbers explain why transplant teams schedule regular skin checks and cancer screenings for their patients, and why researchers keep working on regimens that balance rejection prevention with lower cancer burden.

Chemotherapy That Causes New Cancers

It sounds paradoxical, but some of the drugs used to cure one cancer can cause a different cancer years later. These are called therapy-related or secondary malignancies, and they now make up an estimated 15 to 20 percent of all cancer diagnoses recorded in cancer registries.

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Alkylating agents are the biggest culprits. Patients treated for Hodgkin’s disease, for example, have been reported to face a 20- to 40-fold increased risk of developing secondary acute myeloid leukemia, with that risk climbing alongside the number of treatment cycles and the patient’s age at treatment.

⁵ Different chemotherapy classes leave different fingerprints on the genome. Alkylating agents tend to cause losses of chromosomal material on specific chromosomes, while other agents produce different genetic rearrangements that drive new blood cancers.

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Platinum-based drugs and procarbazine have also been independently linked to secondary gastrointestinal cancers in survivors. In a large study of childhood cancer survivors, platinum drugs were associated with over seven times the risk of a later gastrointestinal cancer, and high-dose procarbazine with about three times the risk.

⁷ The children and young adults treated for a first cancer are especially vulnerable because they have decades of life ahead in which a second malignancy can emerge, and younger tissues appear more sensitive to the DNA-damaging effects of chemotherapy.

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Hormone Therapies and Reproductive Medications

Hormones are powerful growth signals, so it is no surprise that drugs manipulating hormone levels can shift cancer risk in one direction or another. What makes this category complicated is that the same drug can raise risk for one cancer while lowering it for another.

Hormone Replacement Therapy

Estrogen-only hormone replacement therapy, sometimes prescribed for menopausal symptoms, has been linked to a higher risk of endometrial cancer. A large prospective U.S. cohort found that current estrogen-only users had about 1.5 times the risk compared with women who never used HRT, and that risk jumped to nearly three times among women who used estrogen-only therapy for more than ten years. Combining estrogen with progesterone, however, did not carry the same endometrial cancer signal.

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Tamoxifen

Tamoxifen is widely used to treat and prevent estrogen-receptor-positive breast cancer, but it behaves as an estrogen promoter in the uterus. Multiple studies and meta-analyses have confirmed that tamoxifen use increases endometrial cancer risk, particularly with longer duration and higher cumulative doses. One population-based study found that using tamoxifen for three or more years was associated with roughly triple the odds of endometrial cancer.

¹⁰ Earlier research had already pointed in the same direction, finding a significant upward trend in endometrial cancer risk with both longer use and higher cumulative dose of tamoxifen.

¹¹ A systematic meta-analysis pooling data across study designs and continents confirmed the relationship holds broadly, with dose and duration each acting as independent risk factors.

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For most women with estrogen-receptor-positive breast cancer, the survival benefit of tamoxifen still outweighs the endometrial risk. But doctors generally recommend regular gynecological monitoring during and after treatment, and any unusual bleeding should be investigated promptly.

Oral Contraceptives

Birth control pills illustrate the tradeoff principle vividly. A systematic review found they are associated with a modestly increased risk of breast and cervical cancers, but a decreased risk of colorectal and endometrial cancers.

¹³ A large study looking at time-dependent effects found that ever using oral contraceptives was associated with roughly 28 to 32 percent lower odds of ovarian and endometrial cancer, with the protective effect growing stronger with longer use. The increase in breast cancer risk was modest and appeared mainly in women followed up before age 55, with no significant increase over a full lifetime.

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Proton Pump Inhibitors and Stomach Cancer

Proton pump inhibitors like omeprazole, esomeprazole, and lansoprazole are among the most widely prescribed drugs in the world. Their potential connection to gastric cancer has drawn serious attention. A meta-analysis pooling results from multiple epidemiological studies found that PPI users had about 1.8 times the risk of gastric cancer compared with non-users, though the studies varied a lot in their individual estimates.

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The proposed mechanism involves a hormone called gastrin. PPIs work by suppressing stomach acid, and the body responds by producing more gastrin to try to stimulate acid production. Chronically elevated gastrin levels can drive the proliferation of certain cells in the stomach lining, potentially progressing through a sequence of overgrowth, abnormal cell changes, and eventually cancer.

¹⁶ PPIs are the only commonly used drug class that produces sustained elevated gastrin levels at typical clinical doses.

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This does not mean everyone on a PPI should panic. The absolute risk is still small, and many people take these drugs for conditions like severe reflux or Barrett’s esophagus where the benefits clearly outweigh the theoretical cancer risk. The concern is more about the tens of millions of people who take PPIs casually or indefinitely without revisiting whether they still need them. If you have been on a PPI for years without a clear ongoing indication, it is worth discussing with your doctor whether stepping down or switching to a different acid reducer makes sense.

A Common Blood Pressure Pill and Skin Cancer

Hydrochlorothiazide, one of the most commonly prescribed blood pressure medications worldwide, has a photosensitizing effect: it makes skin more vulnerable to ultraviolet radiation. For people who take high cumulative doses over many years, this translates into a real increase in skin cancer risk. A large Danish case-control study found that high cumulative use was associated with about 1.3 times the risk of basal cell carcinoma and roughly four times the risk of squamous cell carcinoma, with a clear dose-response pattern. At the very highest cumulative doses, squamous cell carcinoma risk was over seven times higher.

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A Dutch cohort study found an even sharper association at high cumulative doses, particularly for squamous cell carcinoma, and noted that the signal was strongest among Caucasian adults whose lighter skin already makes them more UV-sensitive.

¹⁹ If you are fair-skinned and have been on hydrochlorothiazide for a long time, sun protection becomes even more important than usual, and asking your doctor about alternative blood pressure medications is reasonable.

Diabetes Medications

Pioglitazone, a diabetes drug in the thiazolidinedione class, has been flagged for a modest but consistent increase in bladder cancer risk. A population-based cohort study found that pioglitazone users had about 1.6 times the risk of bladder cancer compared with people on other diabetes medications, with a dose-response relationship: longer use and higher cumulative doses correlated with greater risk.

²⁰ Multiple meta-analyses have confirmed this. One pooling 19 studies found about a 13 percent increase, and another estimated about 20 percent higher risk in pioglitazone users, with even larger increases when compared specifically against other diabetes drug classes.

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The newer GLP-1 receptor agonists, drugs like semaglutide and liraglutide now widely used for both diabetes and weight loss, generated early concern about thyroid cancer because they caused thyroid tumors in rodents. So far, human data has been reassuring. A systematic review of ten studies found that thyroid cancer incidence in semaglutide users was very low, with isolated cases each constituting less than 1% of study groups.

²³ A comprehensive analysis drawing on clinical trials covering over 100,000 participants, post-marketing surveillance, and a large U.S. commercial database found that while pooled clinical trial data showed a non-significant trend toward more thyroid cancers with GLP-1 agonists compared with placebo, the absolute numbers were tiny and real-world database comparisons showed no increased risk.

²⁴ The rodent-to-human translation appears limited, but given how rapidly GLP-1 use is expanding, this is an area researchers will keep watching closely.

Fertility Drugs

Fertility medications stimulate the ovaries to produce eggs, which means exposing reproductive tissues to intense hormonal signaling. The cancer concern has focused mainly on ovarian and breast cancer. The evidence is mixed but worth knowing about.

For invasive ovarian cancer, the picture is largely reassuring. But for borderline ovarian tumors, a less aggressive form, studies have found a more consistent link. Cohort studies of women undergoing IVF have shown roughly 1.8 to 2.7 times the risk of borderline ovarian tumors compared with subfertile women who did not undergo IVF.

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Clomiphene citrate, one of the oldest and most widely used fertility drugs, has shown some associations that depend on whether the woman eventually became pregnant. In a registry-based cohort study, clomiphene-exposed women who never gave birth had about 2.5 times the risk of ovarian cancer, while those who did become mothers showed no significant increase. Clomiphene was also associated with a modest increase in breast cancer risk among women who had given birth.

²⁶ However, an earlier long-term follow-up study found elevated breast cancer rates only at very low doses and short exposure, with no dose-response pattern, making a causal link uncertain.

²⁷ Untangling the drug’s effect from the underlying infertility itself remains a major challenge in this research.

Herbal Supplements With Hidden Risks

Not all cancer-causing substances come in prescription bottles. Aristolochic acid, a compound found naturally in plants of the Aristolochia genus, has been used in traditional herbal preparations for centuries. It is now recognized as a potent carcinogen. A meta-analysis found that exposure to aristolochic acid was associated with roughly six times the risk of primary urinary tract cancers.

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The danger became dramatically clear in a group of patients in Belgium who had taken a weight-loss supplement containing Aristolochia fangchi. Among 39 patients who agreed to prophylactic surgical removal of their ureters and kidneys, nearly half already had urothelial carcinoma. All tissue samples contained aristolochic acid-related DNA damage, and higher cumulative doses predicted more cancer.

²⁹ Aristolochic acid has since been banned or restricted in many countries, but it can still be found in some herbal products sold online or in poorly regulated markets. This is a case where “natural” does not mean safe.

Contamination Scares and What Actually Happened

In 2018, batches of the blood pressure drug valsartan were found to be contaminated with NDMA, a probable carcinogen. The discovery triggered massive recalls and understandable fear. A nationwide study of 1.4 million valsartan users found that the contaminated versions did not raise overall cancer risk, but they were associated with small, specific increases: about 12 percent higher risk of liver cancer and 10 percent higher risk of melanoma. The researchers estimated this translated to roughly four extra liver cancer cases and six extra melanoma cases per 100,000 person-years of exposure.

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A similar scare hit ranitidine (Zantac), which was pulled from markets over NDMA concerns in 2020. But a Korean nationwide study comparing ranitidine users with users of other drugs in the same class found no increased risk for any cancer type. Higher cumulative doses and longer use of ranitidine did not raise cancer rates either.

³¹ These contamination episodes illustrate that the public fear often outstrips the actual measured risk, though they also show why manufacturing quality control matters for drugs people take every day.

Biologic Drugs for Autoimmune Disease

TNF inhibitors, biologic drugs used to treat rheumatoid arthritis and other autoimmune conditions, have generated debate about cancer risk since they first came to market. Because they suppress part of the immune system, the theoretical concern makes sense. A study of older Americans with rheumatoid arthritis found that TNF inhibitor use was associated with about 32 percent higher risk of non-melanoma skin cancer and 28 percent higher risk of non-Hodgkin lymphoma overall, with a particularly elevated risk of follicular lymphoma at about 2.6 times the baseline rate.

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However, a large Swedish cohort study came to a different conclusion. It found that people starting their first TNF inhibitor had a cancer rate not significantly different from patients on conventional disease-modifying drugs, with an adjusted hazard ratio of 0.93 for invasive solid or blood cancers.

³³ The discrepancy may partly reflect differences in the populations studied and in how long patients were followed. Rheumatoid arthritis itself raises the risk of certain cancers, especially lymphoma, making it hard to separate the disease’s contribution from the drug’s. The current consensus is that any overall cancer risk increase from TNF inhibitors is small, though specific subtypes like skin cancer and certain lymphomas may warrant extra screening.

A Banned Painkiller and Lessons From the Past

Phenacetin, an analgesic that was once a common ingredient in over-the-counter pain relievers, is now banned in most countries because of its link to kidney disease and cancers of the upper urinary tract.

³⁴ A case-control study found that phenacetin-containing analgesic compounds were associated with a 12-fold increase in the risk of renal pelvic cancer. Its metabolite, paracetamol (acetaminophen), did not carry the same risk, suggesting that phenacetin itself, rather than its breakdown products, was the primary carcinogen.

³⁵ The phenacetin story is a reminder that a drug can be widely used for decades before its cancer risk becomes apparent, and that post-market surveillance is essential for catching these slow-developing harms.

Why the Same Drug Affects People Differently

Your personal genetic makeup influences how your body processes medications, and this has real implications for drug-related cancer risk. Variations in drug-metabolizing enzymes can change how quickly a drug is activated, broken down, or cleared from the body. Some people metabolize certain drugs slowly, leading to higher and longer exposure; others metabolize them rapidly, which can either reduce effectiveness or produce more of a toxic byproduct.

One well-studied example involves the CYP2D6 enzyme. Genetic variations in CYP2D6 appear relevant to breast cancer recurrence in women taking tamoxifen, because the enzyme is responsible for converting tamoxifen into its active form.

³⁶ The N-acetyltransferase enzymes are another example: how much of these enzymes your body produces affects your susceptibility to certain drug-induced toxicities and cancers.

³⁷ Genetic differences in drug-metabolizing enzymes can also alter how chemotherapy agents behave, influencing both their effectiveness and the risk of secondary cancers.

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Pharmacogenomic testing is becoming more accessible, and for certain medications like tamoxifen, knowing your metabolizer status can meaningfully change treatment decisions. For most drugs on this list, though, population-level risk data is still the best tool you and your doctor have. The practical takeaway is that the same drug does not carry exactly the same risk for everyone, and in some cases testing can help clarify where you fall on that spectrum.

How Cancer-Causing Drugs Actually Work at the Cellular Level

Not all carcinogenic drugs cause cancer the same way. Some are genotoxic, meaning they damage DNA directly, creating mutations that can start a cell on the path to becoming cancerous. Alkylating chemotherapy agents and drugs like cyclophosphamide fall into this category. Because they interact with DNA, even very low doses are considered to carry some risk, and there is no established “safe” threshold below which cancer cannot occur.

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Others are non-genotoxic: they promote cancer without directly mutating DNA. These drugs work through mechanisms like stimulating cell division, triggering hormonal effects, causing chronic tissue irritation, or making epigenetic changes that alter gene activity. Estrogen-only HRT and PPIs likely fall into this camp. Because non-genotoxic carcinogens do not damage DNA directly, they are generally thought to have a safe threshold below which cancer risk does not increase meaningfully.

⁴⁰ This distinction matters practically: for drugs in the non-genotoxic category, using the lowest effective dose for the shortest necessary time is likely to minimize risk. For genotoxic agents, the calculus is different and the risk of future cancer often has to be accepted as part of a life-saving treatment.

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