Lead blood levels may increase smokers’ risk for kidney cancer

Higher than normal levels of lead in the blood may signal a risk two times higher than average of developing renal cell carcinoma in smokers, according to medical researchers.

“Past studies (in cadavers) have shown that, compared with kidneys from individuals without cancer, kidneys from individuals with cancer have higher lead levels,” said Emily B. Southard, medical student at Penn State College of Medicine. “But prior to this study, the identification of higher lead in blood as a risk factor among healthy individuals before they develop kidney cancer had not been shown.”

Southard, working with Robin Taylor Wilson, associate professor of public health sciences at the College of Medicine, analyzed data collected from the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to measure levels of blood lead, calcium and vitamin D in stored blood donated by healthy individuals several years before renal cell carcinoma ever developed.

According to the National Institutes of Health, renal cell carcinoma is the most common type of kidney cancer in adults, accounting for 92 percent of kidney cancers. The National Cancer Institute of the NIH predicted that there would be about 56,000 new cases of RCC in 2011 and has reported that nearly 300,000 people in the United States are living with kidney cancer today.

In previous studies involving animals, researchers had found an inverse correlation between the amount of lead retained in the body and the amount of calcium in the diet. This supports the hypothesis that higher calcium levels in the body can reduce lead retention. While Southard and Wilson also found that levels of calcium were higher in men who had a lower risk of kidney cancer, there was not a strong correlation between blood levels of lead and blood level of calcium or 25-hyrdoxyvitamin D. Therefore, they could not conclude that calcium or vitamin D levels had an influence on the risk observed related to blood lead levels.

Southard and Wilson looked at whether the subjects had ever been in a “high-risk occupation,” which would expose the subject to more lead than an average person - such as mining, asbestos fabric manufacture or oil refining.

“There were no significant differences in occupational history or smoking history between cases and controls in our study that would sufficiently explain the association we observed,” the researchers reported online in Cancer Epidemiology, Biomarkers and Prevention.

Pulling together data from 24 studies conducted since the 1960s, an international research team found that the risk of kidney cancer was 38 percent higher among people who had ever smoked versus those who had never picked up the habit.

And the more smokers had puffed over a lifetime, the greater the risk to their kidneys — a so-called dose-response relationship that supports a direct link between smoking and kidney cancer.

In fact, Hunt told Reuters Health, before conducting this study, he had been skeptical that the relationship between smoking and kidney cancer was real - in part because past studies have yielded conflicting results. Even when an association has been found in individual studies, he noted, it has generally been “modest.”

Hunt and his colleagues culled data from 24 previous studies conducted in North America, Europe and Australia, and used a mathematical model to estimate the overall risk of kidney cancer associated with various levels of smoking.

The researchers found that among men, those with a history of smoking were more than 50 percent more likely to develop kidney cancer than those who had never smoked. Among women, smokers had a 22 percent greater risk of developing the disease. Even light smokers - those who averaged fewer than 10 cigarettes a day - were 60 percent more likely than non-smokers to develop the disease. The odds were still higher with moderate smoking, defined as 10 to 20 cigarettes per day.

- Jay D. Hunt, Ph.D, International Journal of Cancer, 10 March 2005

The ATBC study consisted of nearly 30,000 Finnish male smokers between the ages of 50 and 69 years, enrolled from 1985 to 1988. The study was initially conducted to study lung cancer prevention. This study collected blood samples periodically for over two decades. Finland has a cancer registry that tracks patients, making it easier to follow up with patients after diagnosis than it is in the United States.

Southard, Wilson and colleagues looked at a cohort within the ATBC study that included 154 renal cell carcinoma cases, diagnosed after the initial blood collection, and 308 controls. Notably, Southard and Wilson found that among renal cancer cases alone, those with higher blood levels of calcium and vitamin D had a longer period of time before they developed cancer, as measured from blood when they first enrolled in the study as healthy individuals.

“This association suggests that vitamin D and calcium biomarkers may be important clues that can lead us to the early diagnosis of cancer,” said Wilson. This is important because there are currently no available screening tests for kidney cancer.

Kidney Cancer Prognosis and Smoking

If caught early, the prognosis for kidney cancer is good, and the chance for survival is high. Even tumors that have spread beyond the kidneys are often treatable.

An individual who smokes and has received a kidney cancer diagnosis can still make lifestyle changes that better his chances for a successful outcome. Smokers who have been diagnosed with kidney cancer should:

  Eat a diet that is rich in protein and fiber and low in sugar and fat.
  Get regular exercise. Talk to your doctor about establishing an exercise program that is healthy for your particular case.
  Talk to their doctors about methods to help them quit smoking.
  Use stress-reduction therapies to improve both mind and body. These therapies are especially helpful to those who are trying to quit smoking.

“Studies have shown that people with kidney cancer have higher average lead levels in their kidney tissue, compared with people without kidney cancer,” said Southard. “Prior to our study, this was only shown in cadavers and not in living people. Now we have shown that elevated blood lead levels put smokers at higher risk for renal cell carcinoma.”

Further work is in progress by Penn State investigators to identify risks among women and non-smokers to find early detection biomarkers.


Working with Southard and Wilson were Alanna Roff, research associate; Tracey Fortugno, research associate; John P. Richie Jr., professor of public health sciences; Matthew Kaag, M.D., assistant professor of surgery; Vernon M. Chinchilli, Distinguished Professor and Chair of public health sciences, all at Penn State College of Medicine; Jarmo Virtamo, research professor at the National Institute for Health and Welfare, Helsinki, Finland; Demetrius Albanes, M.D., senior investigator, division of cancer epidemiology and genetics, National Cancer Institute; and Stephanie Weinstein, division of cancer epidemiology and genetics, National Cancer Institute.

The American Institute for Cancer Research and the Pennsylvania Department of Health Tobacco Settlement Fund supported this work.


Victoria M. Indivero
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Penn State

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