Kidney cancer is one of the 10 most-diagnosed cancers in the United States. Like many of the other cancers on that list—including colon and rectal cancer—kidney cancer is more common now than it used to be. But unlike some others, the underlying causes of kidney cancer are often hard to discern.
For example, a significant proportion of breast cancers stem from inherited genetic mutations. But that’s not the case for kidney cancer. Just 3% to 5% of these cancers are caused by hereditary factors. “There are certain genetic conditions associated with increased risk, but the vast majority of kidney cancers are not familial-based,” says Dr. Shilajit Kundu, chief of urologic oncology at the Northwestern University Feinberg School of Medicine. “Patients always ask me, ‘Why did I get this?’ And it’s tough to give them an answer,” Kundu adds. “I often say it’s just bad luck.”
The medical term he and other cancer experts use for this kind of bad luck is “sporadic,” meaning the disease tends to appear randomly without any obvious cause. However, not all kidney cancers arise out of the blue. There are a handful of established risk factors, including exposure to some known carcinogens. There are also demographic factors—such as biological sex and race—associated with increased risks.
Here, Kundu and other kidney cancer experts detail medical science’s current understanding of these risk factors, plus how it may be possible to lower your risk for the disease.
A familiar culprit
When people hear the words “smoking” and “cancer” in the same sentence, they often assume that the topic is lung cancer. But smoking is also an established risk factor for several other cancers, and that includes cancers of the kidney.
While the likelihood that a smoker develops kidney cancer is relatively small, researchers have estimated that smoking increases a person’s risk for the disease by 20-50%. “When you inhale the carcinogens in tobacco, they are absorbed through the lungs into the bloodstream,” explains Dr. Zachary Smith, a kidney cancer specialist at Washington University in St. Louis. It’s the job of the kidneys to clean and filter blood. If that blood contains tobacco carcinogens, some of those are going to end up in the kidneys, where they could contribute to a cancer-causing mutation, he explains.
Smoking may also promote kidney cancer in some indirect ways. For example, smoking can cause high blood pressure, which is another risk factor for kidney cancer. (More on that in a minute.) “This is one of the few modifiable risk factors for the disease that a person can control,” Smith says.
Men are at greater risk
In 2022, approximately 80,000 Americans were expected to be diagnosed with kidney cancer. More than 50,000 of those new cases—well over 60%—will arise in men. “Being male increases your risk for kidney cancer almost two-fold,” says Dr. Daniel George, a kidney cancer specialist and professor of medicine at the Duke University Cancer Center.
For a time, there was speculation that smoking may account for these sex-based risk discrepancies. (Traditionally, men have smoked more than women.) However, that tobacco hypothesis was not borne out by close research scrutiny, and new theories have taken its place. “There seems to be a hormonal basis to kidney cancer,” George says. “The incidence in premenopausal women is much lower than in men of that age, but after menopause the incidence starts to balance out.”
The female sex hormone estrogen may help explain risk inequalities. Prior to menopause, women tend to have much higher estrogen levels than men. Some research has found that estrogen can help replace damaged kidney cells, and the cyclical shifts in estrogen brought on by a woman’s menstrual cycle may also promote kidney health. “This is one theory that has some evidence to support it,” George says.
Associations with hypertension and obesity
Study after study has found that people with hypertension are at elevated risk for kidney cancer. The higher a person’s blood pressure, the greater their odds of developing the disease. These correlations persist even after researchers have controlled for obesity, medication use, and other confounding explanations.
While the connection between hypertension and kidney cancer is well-established, experts aren’t sure exactly how high blood pressure contributes to the development of the disease. “We know the association is there, but the exact causality isn’t clear,” Kundu says. One theory is that hypertension may induce a state of chronic inflammation, which may impair kidney health in several ways that could elevate kidney cancer risk. Hypertension could also lead to the formation of blood molecules called reactive oxygen species, which can encourage tumor development and progression.
There’s evidence that hypertension also accounts for racial disparities in kidney cancer risk. For example, Black Americans are significantly more likely than white Americans to develop kidney cancer. Some researchers have determined that by taking steps to reduce rates of hypertension—another condition that’s more common among Black Americans—the racial differences in kidney cancer risk would level out.
Hypertension often goes hand-in-hand with obesity, which is another major risk factor for kidney cancer. According to some estimates, excess body weight accounts for up to 40% of kidney cancer cases. There’s also evidence that the connection here is dose dependent, meaning a person’s risk for kidney cancer rises as their weight increases. (Rates of kidney cancer have been climbing for decades, both in the U.S. and other parts of the world, and experts have speculated that increasing rates of obesity may explain this trend.)
But here again, the exact mechanisms linking body weight to kidney cancer are not well elucidated. “Obesity is a risk factor for multiple malignancies, including kidney tumors, but we don’t exactly know the mechanisms there,” Smith says. Excess body weight can lead to endocrine (hormonal) shifts that may contribute to the development of kidney cancers. Insulin resistance and blood-oxygen imbalances caused by excess weight could also be factors. It’s possible that these and other weight-related biological changes could ultimately explain the obesity-kidney cancer connection, but more work is needed.
Hereditary risk factors
Again, only a small percentage of kidney cancers—roughly 3% to 5%—are caused by inherited genetic mutations. So far, researchers have identified at least 12 heritable genes or mutations that can be passed down within families that increase the risk of kidney cancer.
People who carry these genes are more likely to develop the disease earlier in life. “Particularly in younger patients”—those under the age of 40—“we do check for genetic risk factors,” says George.
The best-studied of these heritable mutations is associated with a syndrome called von Hippel Lindau (vHL) disease. People who carry the vHL gene—about 1 in 35,000 worldwide—have a 70% likelihood of developing kidney cancer by age 50, and are almost certain to develop kidney cancer at some point in their lifetime. However, a majority of these vHL cancers are identified early, before they’ve spread to other parts of the body, and only about 1 in 3 people with the vHL gene will go on to develop metastatic cancer.
A 2020 analysis in the journal Environmental Science & Technology found that there are more than 150,000 individual chemicals registered for commercial use. Mapping the short- and long-term health effects of exposures to these chemicals, either alone or in combinations, is an immense challenge. But researchers have already established that some chemical exposures are risk factors for kidney cancer.
One example is trichloroethylene (TCE), a solvent primarily used to degrease machine parts. (Less commonly, TCE also turns up in chemicals used in the dry-cleaning, leather-processing, agricultural, and electronics industries.) The U.S. Environmental Protection Agency has classified TCE as “carcinogenic to humans,” and some studies have found that people exposed to heavy amounts of TCE at work (mostly those working in industrial manufacturing prior to the 1980s) are up to 50% more likely to develop kidney cancer than those not exposed.
Thanks to the research linking TCE to cancer, the chemical has been largely phased out of use. However, experts say other chemical exposures are likely to emerge as kidney cancer risk factors. “The kidneys are our filters, and so any chemicals we ingest or absorb or inhale can end up concentrated in them,” says George.
Some preliminary research has found that environmental toxins such as nitrate and radon—which can turn up in drinking water—may also raise a person’s risk for kidney cancer. “The longer I’ve been an oncologist, the more I’ve become kind of a hippie when it comes to chemical exposures,” Smith says. “Everyone is paying attention to the things used in heavy industrial processes or agricultural pesticides, but I think there are other things in our environment now—in our food or in our homes or workplaces—that are going to be revealed over time as risk factors.”
How to lower your risks
Some of the risk factors mentioned above are “modifiable,” meaning people have some control over them. “Avoiding smoking is a big one,” Smith says. Other experts echo his advice, and add that generally healthy living—such as avoiding processed foods and getting plenty of exercise—could also make a difference.
There’s some evidence, albeit limited, that the more a person exercises, the less likely they are to develop kidney cancer. There’s also research showing that people who eat diets rich in whole fruits and vegetables are at reduced risk for the disease. Avoiding processed meats (such as deli meats like salami and smoked sausage) may also lower your risks.
Surprisingly, there’s a fair amount of work linking alcohol consumption to a reduced risk for kidney cancer. According to a 2018 research review in the Journal of Clinical Oncology, a handful of studies have found that moderate drinkers—usually defined as those who have one to two drinks per day—lower their risk for kidney cancer by 20% compared to lighter drinkers or non-drinkers. However, alcohol consumption on the whole is associated with an increased risk for cancer—including cancers of the breast, esophagus, liver, and colon. If you’re concerned about cancer, drinking less (or not at all) seems to be the best approach.
While there are things a person can do to reduce their cancer risks, experts reiterate that kidney cancer is a complex disease that often stems from a combination of factors. “If people can use this as motivation to develop healthier habits, that’s great, but I wouldn’t go so far as to tell them they can prevent kidney cancer,” George says. “We’ve identified some important risk factors and trends, but more research is needed to understand why the incidence is rising.”
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Contributor: Markham Heid