High intake of ingredients known as nitrite and nitrate added to processed meats to aid preservation may be tied to bladder cancer -- but the relationship appears to be tentative, researchers say.
In a study that followed more than 300,000 men and women for seven years, dietary nitrite and nitrate, as well as nitrite alone, were associated with an increased risk of bladder cancer among individuals with the highest consumption of processed meat -- but the connection was of borderline statistical significance, according to Amanda J. Cross of the National Institutes of Health and colleagues.
In other words, the findings may have more to do with chance alone than with an actual causal link.
Consumption of processed meat itself was not associated with an increased risk of bladder cancer, Cross and colleagues reported in the journal Cancer.
"I think we should approach these modest results with caution," Dr. Shilajit Kundu, chief of urologic oncology at Northwestern Memorial Hospital, said in an interview with MedPage Today. Kundu was not involved in the study.
Nathan Bryan of the University of Texas, who also was not involved in the study, had similar concerns.
"There is not one single bit of data presented that is statistically significant by conventional statistical rules with 95 percent confidence," he said in an email to MedPage Today and ABC News. "With over 300,000 subjects, statistical significance should not be a problem if there is a clear and indisputable association."
Researchers suspect that meat could be involved in bladder cancer due to compounds related to cooking and processing, including nitrates, nitrites, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs).
Nitrate and nitrite are added to processed meat for preservation as well as enhancement of color and flavor. PAHs and HCAs can form during cooking.
These compounds and their metabolites are excreted through the urinary tract, which could lead to the development of cancer through contact with the cells lining the bladder or through systemic exposure, the researchers said.
Yet evidence from prospective studies of meat and bladder cancer has been inconsistent.
So the researchers looked at data 300,933 patients in the NIH-AARP Diet and Health Study, which included a food frequency questionnaire. Using various databases of nutritional information, they estimated intakes of nitrate, nitrite, HCAs, and PAHs.
Over seven years of follow-up, there were 854 cases of transitional cell bladder cancer.
The researchers found that, compared with those who ate the least amounts of red meat those who ate the most had a 22 percent higher risk of bladder cancer, though the finding was of borderline statistical significance. The researchers said the relationship was driven by consumption of processed red meats.
However, there was no association between bladder cancer and white meat or processed meat itself.
There was also no association between bladder cancer and beef, bacon, hamburger, sausage, or steak -- but the researchers did find a positive association for cold cuts made from red meat.
While bladder cancer and nitrate were not linked, there was an association with dietary nitrite. Those with the highest nitrite consumption had an increased risk compared with those with the lowest intake -- but again this finding did not reach the traditionally accepted level of statistical significance.
Still, Cross and colleagues said the findings "support the hypothesis of 'N-nitroso compounds' involvement in bladder carcinogenesis, as processed meat also provides amines and amides necessary for the endogenous formation of [these compounds]."
The researchers said the findings "provide modest support" for an increased risk of bladder cancer associated with nitrite plus nitrate and PhIP, but acknowledged that the study was limited by a lack of information on urination frequency and bladder infections and limited data on beverage intake.
The authors called for further research into different dietary sources of nitrate and nitrite to determine which may have the strongest association with bladder cancer.
"Additional research is needed to confirm our findings of a possible increased risk of bladder cancer with intake of red meat and especially for PhIP, as prospective investigations of meat-related mutagens and this malignancy are lacking," they added.
Kundu told MedPage Today that "a lot of work still needs to be done before we can say that red meats or processed meats should be cut out all together."