Factors Increase the Risk-of Kidney Cancer

Kidney cancer is one of the top 10 most common types of cancer in the US. Like many other cancers on that list, like colon and rectal cancer, kidney cancer is more common now than it used to be. However, unlike certain other cancers, the underlying causes of kidney cancer are frequently challenging to determine.

For example, inherited genetic mutations cause a significant proportion of breast cancers. However, this is not the case with kidney cancer. Hereditary factors are responsible for only 3% to 5% of these malignancies. “There are specific hereditary abnormalities associated with greater risk,” says Dr. Shilajit Kundu, chief of urologic oncology at Northwestern University Feinberg School of Medicine. “Patients are continually asking me, ‘How did I get this?'” And it’s difficult to respond,” Kundu continues. “I frequently say it’s just terrible luck.”

He and other cancer doctors refer to this type of poor luck as “sporadic,” which means the disease appears randomly with no evident cause. However, not all kidney malignancies occur out of nowhere. A few identified risk factors include exposure to some known carcinogens. Additional demographic characteristics are associated with elevated risks, such as biological sex and race.

Kundu and other kidney cancer experts explain how medical science now understands these risk factors, as well as how you may be able to reduce your risk of the disease.

A familiar culprit

People frequently think that when they hear the terms “smoking” and “cancer” in the same sentence, the topic is lung cancer. However, smoking is a known risk factor for various other malignancies, including kidney cancer.

While it is unlikely that a smoker may acquire kidney cancer, researchers estimate that smoking increases a person’s disease risk by 20-50%. “When you inhale the cancer-causing chemicals in tobacco, they get into your bloodstream through your lungs,” says Dr. Zachary Smith, an expert on kidney cancer at Washington University in St. Louis. The kidneys’ role is to clean and filter blood. He explains that if the blood includes tobacco carcinogens, some will wind up in the kidneys, which may contribute to a cancer-causing mutation.

In several instances, smoking may indirectly induce kidney cancer. Smoking, for example, can result in high blood pressure, another risk factor for kidney cancer. “This is one of the few modifiable illness risk factors that a person can control,” Smith adds.

Men are at greater risk

Around 80,000 Americans are predicted to have kidney cancer by 2022. More than 50,000 of those additional cases, or over 60%, will be men. “Being a man practically doubles your chance of kidney cancer,” says Dr. Daniel George, a kidney cancer specialist and professor of medicine at Duke University Cancer Center.

For a time, it was thought that smoking was to blame for these sex-based risk disparities. (Historically, men smoked more than women.) However, close study inspection did not support the tobacco hypothesis, and new theories have taken place. “Kidney cancer appears to have a hormonal foundation,” George explains. “The incidence is substantially lower in premenopausal women than in men of that age, but after menopause, the incidence begins to balance out.”

The female sex hormone estrogen may aid in explaining risk disparities. Women have substantially higher estrogen levels than men before menopause. According to some studies, estrogen can help repair damaged kidney cells and the cyclical changes in estrogen caused by a woman’s menstrual cycle may also enhance kidney health. “This is one notion with some evidence behind it,” George explains.

Associations with hypertension and obesity

According to study after study, people with hypertension are at an increased risk of developing kidney cancer. The higher a person’s blood pressure, the more likely they will get the condition. These associations continue even after researchers account for weight, pharmaceutical use, and other potential confounding factors.

While the link between hypertension and kidney cancer is well recognized, researchers aren’t sure how high blood pressure leads to the disease’s development. “We know there is a correlation, but the specific causality is unclear,” Kundu explains. According to one idea, hypertension may cause chronic inflammation, damaging kidney health in various ways and potentially increasing the risk of kidney cancer. Hypertension may also cause the creation of blood molecules known as reactive oxygen species, which can promote tumor growth and progression.

There is evidence that hypertension contributes to racial differences in kidney cancer risk. Black Americans, for example, are substantially more likely than white Americans to have kidney cancer. Some researchers believe that reducing hypertension rates—another more frequent illness among Black Americans—would even out racial inequalities in kidney cancer risk.

Obesity, another critical risk factor for kidney cancer, frequently coexists with hypertension. According to some estimates, excess body weight may cause up to 40% of kidney cancer incidences. There is also evidence that the link is dosage dependent, which means that a person’s risk of kidney cancer increases as their weight increases. Kidney cancer rates have been rising for decades in the United States and other parts of the world, and experts have theorized that rising obesity rates may explain this trend.

However, the precise processes linking body weight to kidney cancer are still unknown. “Obesity is a risk factor for a variety of cancers, including kidney tumors, but the causes are unknown,” Smith explains. Excess body weight can cause endocrine (hormonal) changes that can contribute to kidney cancer development. Excess weight may also induce insulin resistance and blood-oxygen imbalances. These and other weight-related biochemical alterations could eventually explain the obesity-kidney cancer link, but further research is needed.

Hereditary risk factors

Again, inherited genetic abnormalities generate just a small number of kidney cancers—roughly 3% to 5%. Researchers have discovered at least 12 heritable genes or mutations that can be passed down through families and raise the risk of kidney cancer.

People with these genes are more likely to get the disease at a younger age. “We do examine for genetic risk factors in younger patients,” meaning those under 40, according to George.

The well-studied of these heritable mutations is linked to von Hippel Lindau (VHL) illness. People who carry the vHL gene, which affects around 1 in 35,000 people globally, have a 70% chance of acquiring kidney cancer by age 50 and are nearly sure to develop kidney cancer at some point in their lives. However, the vast majority of these vHL malignancies are detected early, before they spread to other body areas. Only one in every three persons carrying the vHL gene will develop metastatic cancer.

Chemical exposures

According to a 2020 study published in the journal Environmental Science & Technology, there are over 150,000 different chemicals registered for commercial use. Mapping these substances’ short- and long-term health impacts, either alone or in combination, is a massive undertaking. However, scientists have already determined that some chemical exposures are risk factors for kidney cancer.

Trichloroethylene (TCE), a solvent predominantly used to degrease machine parts, is one example. TCE is also found in chemicals used in the dry-cleaning, leather-processing, agricultural, and electronics industries, though less frequently. It has been classed as “carcinogenic to humans” by the US Environmental Protection Agency, and some studies have revealed that those exposed to high levels of TCE at work (primarily in industrial production before the 1980s) are up to 50% more likely to acquire kidney cancer than those who are not.

TCE has been mostly fazed out of use due to research associating it with cancer. Other chemical exposures, however, are expected to emerge as risk factors for kidney cancer, according to specialists. “Because the kidneys are our filters, any substances we ingest, absorb, or inhale might end up concentrated in them,” George explains.

Some preliminary study suggests that environmental contaminants like nitrate and radon, which can be found in drinking water, may increase a person’s risk of kidney cancer. “The longer I’ve been an oncologist, the more hippies I’ve been in terms of chemical exposures,” Smith adds. “Everyone is paying attention to what is used in heavy industrial processes or agricultural pesticides, but I believe there are other things in our environment now—in our food, homes, or workplaces—that will be disclosed as risk factors over time.”

How to lower your risks

Some of the risk variables described above is “modifiable,” which means they can be changed. “One significant one is not smoking,” Smith explains. Other specialists agree with him, adding that basic healthy living, such as avoiding processed meals and getting enough exercise, may also help.

There is some, albeit limited, evidence that the more a person exercises, the less likely they are to get kidney cancer. There is also evidence that persons who consume a diet high in whole fruits and vegetables have a lower risk of developing the disease. Avoiding processed meats (such as salami and smoked sausage) may reduce your risks.

Surprisingly, there is a substantial body of research associating alcohol consumption with a lower risk of kidney cancer. According to a 2018 research review published in the Journal of Clinical Oncology, moderate drinkers—those who consume one to two drinks per day—have a 20% lower risk of kidney cancer than lighter drinkers or non-drinkers. However, alcohol intake, in general, is linked to an increased risk of cancer, including breast, esophageal, liver, and colon cancers. If you’re worried about cancer, drinking less (or not at all) is the best solution.

While there are steps a person can take to lower their cancer risk, experts emphasize that kidney cancer is a complex disease that is often caused by a combination of factors. “It’s great if individuals can use this as motivation to create healthy habits, but I wouldn’t go so far as to suggest they can prevent kidney cancer,” George says. “We’ve discovered some critical risk variables and trends, but additional research is required to understand why the prevalence is increasing.”


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