We recently completed a case-control study of renal cell carcinoma (RCC) among Los Angeles County residents, which is by far the largest population-based study of this rare cancer ever conducted in a single, geographically defined study population. With 1204 incident cases of renal cancer and an equal number of population control subjects, we were one of the first to provide detailed and relatively precise quantification of the modest effect of cigarette smoking on renal cancer development. We estimate that 17% of renal cell carcinoma (21% in men, 11% in women) in Los Angeles can be attributed to cigarette smoking.

This study also definitively established obesity and hypertension as major risk factors for renal cell cancer. Little is known about possible mechanism(s) by which obesity and hypertension lead to renal cell cancer development. We proposed and provided experimental support for the hypothesis that increased lipid peroxidation of the target cells (i.e., proximal renal tubules) in obese and hypertensive individuals is responsible for the high risk of renal cancer among these two groups of individuals.

The large-scale RCC study was specifically designed to examine risk in relation to medication use, especially lifetime intake of diuretics/anti-hypertensives, diet pills including amphetamines, and both over-the-counter and prescription analgesics. Our results suggest that diuretic intake is not an independent risk factor for renal cancer, but rather the consequence of the strong and direct association between hypertension and renal cancer. On the other hand, our data strongly implicate sustained use of analgesics, irrespective of chemical formulation, as a causal factor in renal cancer development. We estimate that 18% (15% in men, 25% in women) of RCC in Los Angeles can be attributed to this iatrogenic exposure. Regular use of amphetamines is another iatrogenic risk factor for renal cancer in Los Angeles, although only a small fraction (about 5%) of cases are related to this putative renal carcinogen.

Relatively few epidemiologic studies have examined the role of diet in RCC. In Los Angeles, we found a strong inverse association between intake of cruciferous vegetables and risk. In terms of nutrients, there were significant inverse associations with intake of various carotenoids. Interestingly, we noted a significant residual effect of cruciferous vegetables on risk after adjustment for carotenoid intake, suggesting that other protective compounds may be present in these vegetables.