During 1,922,817 person-years of follow-up, we identified 854 transitional cell bladder cancers (720 men, 134 women). Individuals consuming the most red meat were younger, less educated and physically active, and had lower intakes of fruits, vegetable, and vitamins C and E than those consuming the least (). Those in the highest quintile of red meat compared to those in the lowest were more likely to be non-Hispanic white, current smokers, to have a higher BMI, and to have higher intakes of beverages and total energy.
Means and proportions of baseline characteristics by red meat quintiles (g/1000kcal) (n=300,933).
We observed a borderline statistically significant increased risk of bladder cancer for those in the highest versus the lowest quintile of red meat (HR=1.22, 95% CI=0.96–1.54, p-trend= 0.07), but no association with white meat or processed meat (). The red meat association was driven by processed red meats (HR for fifth compared to first quintile=1.30, 95% CI=1.00–1.69, p-trend=0.17), rather than non-processed red meats (HR=1.08, 95% CI=0.84–1.38, p-trend=0.22) (data not shown). There were no associations with beef, bacon, hamburger, sausage, or steak; however, we did observe a positive non-linear association for red meat cold cuts (HR for fifth compared to first quintile=1.42, 95% CI=1.10–1.84, p-trend=0.18) (data not shown). Analyses using residual energy adjustment (g/day) resulted in a similar association for red meat (HR=1.17, 95% CI=0.93–1.47, p-trend=0.10) and a slightly stronger association for processed meat (HR=1.14, 95% CI=0.91–1.43, p-trend= 0.06). Including squamous cell carcinomas, adenocarcinomas, and not otherwise specified carcinomas of the bladder (an additional 113 cases) did not alter risk estimates. There was also no evidence of effect modification for the meat exposures by gender, smoking, or beverage intake (data not shown).
Distribution and HRs with 95% CIs for bladder cancer risk within quintiles of meat (g/1000 kcal).
We saw no clear association for total dietary nitrate (HR=0.80, 95% CI=0.58–1.10, p-trend=0.28). However, total dietary nitrite was positively associated with bladder cancer in the top quintile (HR=1.28, 95% CI=1.02–1.61), although the p for linear trend was only borderline statistically significant (p-trend=0.06) (). We observed a suggestive positive association with measured values of nitrate from processed meat, but this association failed to reach statistical significance in the highest quintile (HR=1.20, 95% CI=0.95–1.51, p-trend=0.06). There was no clear association with measured values nitrite from processed meat and bladder cancer (HR=1.07, 95% CI=0.85–1.36, p-trend=0.79). However, we observed a borderline statistically significant association for combined nitrate and nitrite from processed meat among those in the top quintile (HR=1.29, 95% CI=1.00–1.67, p-trend=0.11).
Distribution and HRs with 95% CIs for bladder cancer risk within quintiles of nitrate and nitrite (mg/1000 kcal).
There was no evidence of effect modification for the nitrate and nitrite exposures by gender, beverage intake, smoking, or vitamin C intake (data not shown). In addition, excluding individuals who may have had substantial exposure to nitrate from drinking water (n=7,085) due to residence in an area with high nitrate ground water levels did not alter our risk estimates (data not shown).
DiMeIQx, MeIQx, B[a]P, and mutagenic activity were not associated with bladder cancer, but there was suggestive increased risk with PhIP (HR=1.19, 95% CI=0.95–1.48, p-trend= 0.06) (). There was no association between grilled (top vs. bottom tertile HR=0.97, 95% CI=0.82–1.15, p-trend=0.50), pan-fried (HR=1.02, 95% CI=0.86–1.22, p-trend=0.79) or well/very-well done (HR=1.03, 95% CI=0.86–1.23. p-trend=0.33) meat and bladder cancer (data not shown).
Distribution and HRs with 95% CIs for bladder cancer risk within quintiles of meat mutagens.