In this study, hypertension was associated with an elevated risk of renal cancer in both blacks and whites. Renal cancer risk increased with increasing time since hypertension diagnosis in both races, with stronger effects in blacks. A similar pattern was observed for decreasing levels of blood pressure control. When both race and sex were considered, black women had the strongest association of hypertension with renal cancer.
We know of no previous studies that have considered the association of hypertension and renal cancer among blacks. The two-fold risk observed among whites is similar to findings from many cohort12–15
studies. Our finding of increasing renal cancer risk with decreasing blood pressure control is consistent with prospective cohort studies reporting higher renal cancer risks with higher blood pressure measurements at baseline.15,24–26
Furthermore, in a cohort of Swedish men, a reduction in blood pressure over time was associated with a decrease in renal cancer risk, suggesting that effective hypertension control may lower risk.25
The effect of hypertension duration on renal cancer risk has been examined mainly in case-control studies, with some reports of higher risks at longer durations,18,21
some of no association,19,22,23
and some of higher risks at durations of ≤5 years.17,27
Our finding that years since hypertension diagnosis and level of blood pressure control both independently affect renal cancer risk appears new; we know of no other study with information on both factors.
The biologic mechanisms underlying the hypertension-renal cancer association are unclear; hypotheses include lipid peroxidation and formation of reactive oxygen species,1,28
and up-regulation of hypoxia-inducible factors due to the chronic renal hypoxia that accompanies hypertension.1,15,29–31
We compared hypertension histories among controls to the U.S. population using NHANES data (1999–2004).3
For consistency, we considered NHANES participants to be hypertensive only if they were already aware of their condition at the time of interview. The prevalence of hypertension among controls aged 50–79 years was comparable to that estimated based on NHANES data; differences within race and sex subgroups were generally small (black men: 55% in NHANES vs. 53% in our study; white men: 37% vs. 43%; black women: 63% vs. 58%; white women: 43% vs. 36%). For ages 20–49 years, when the occurrence of hypertension is low, the differences were pronounced for black men (11% in NHANES vs. 27% in our study) and black women (17% in NHANES vs. 6% in our study). Excluding those younger than age 50 from our analysis raised ORs for black men and lowered ORs for black women, but did not alter our conclusions. This provides evidence that our results are unbiased.
A source of controversy has been whether the hypertension-renal cancer association arises from the hypertension itself or from the use of antihypertensive medications. Although antihypertensive drugs have been associated with elevated renal cancer risk, recent studies have concluded that this is likely confounded by a history of hypertension.1,12,15,25,32,33
Renal cancer risk was not elevated among 156 normotensive individuals in our study who took prescription drugs with antihypertensive properties for conditions other than hypertension. This observation supports the position that renal cancer risk is increased by hypertension rather than by its treatment. Our observation that renal cancer risks are highest when blood pressure is poorly controlled also suggests that hypertension is the responsible factor. Further analysis of data collected in this study will examine whether specific types of antihypertensive mediations influence renal cancer risk.
In our study, most of the unmedicated hypertensive subjects had been diagnosed with hypertension only recently (60% within five years of the reference date, compared with 27% of individuals who were medicated). Their blood pressure, when first rechecked by the diagnosing health care provider, was often found to be acceptable (25%) or borderline (50%), possibly indicating that they were not truly hypertensive or that their condition was mild enough to be controlled with life-style changes. It is, however, difficult to explain the reduced renal cancer risk that we observed among unmedicated hypertensives. Compliance with physician-recommended life-style changes might have protected against renal cancer, but this is speculative. This finding is also based on a relatively small number of cases and controls, and chance variation is possible.
If the hypertension-renal cancer relationship observed in our study is causal, our calculations provide a rough upper bound on the potential benefits of hypertension control. If, hypothetically, it were possible to prevent hypertension entirely, we estimate that, among those aged 50–79, renal cancer incidence could be reduced by 44% and 35% among black and white men, and that the male racial disparity in renal cancer incidence in this age group could be reduced by 66%. Among women, our analysis suggests that renal cancer incidence in the absence of hypertension could be reduced by 51% and 30% for blacks and whites, respectively, and that the racial disparity could be reversed, with white women having higher incidence rates than black women. Clearly, preventing hypertension entirely is not an achievable goal. However, these estimates illustrate the substantial role that hypertension likely plays in the black-white disparity in renal cancer incidence rates.
Our study is, to our knowledge, the first renal cancer case-control study with enough blacks to evaluate the hypertension-renal cancer risk relationship by race. Another strength is the detailed information on hypertension, allowing evaluation of renal cancer risk according to both time since hypertension diagnosis and extent of hypertension control. Information on smoking, BMI, and family history of cancer allowed adjustment for potential confounders. Histologically-confirmed cancers and a large sample size are additional strengths.
An important limitation of the study was the need to rely on binary classification of hypertension because information on the severity of hypertension (blood pressure measurements, for example) was unavailable. NHANES data from 1999–2002 show that hypertensive blacks had slightly higher blood pressures than hypertensive whites (142/79 vs. 140/75, respectively), with a wider gap among the subset taking antihypertensive medication (141/77 for blacks, 137/72 for whites).34
If renal cancer risk is higher for people with higher blood pressure, as evidence suggests,15,24–26
the higher blood pressures among hypertensive blacks (especially those with inadequate treatment) could explain the higher odds ratios observed among blacks compared with whites.
Another limitation is that hypertension and medication histories were based on self-report. Some hypertensive persons were likely unaware of their condition.3
We addressed this to some extent by excluding those whose blood pressure was never measured. If more cases than controls were aware of their hypertension, we might have overestimated the hypertension-renal cancer association and the PARs. However, the similarity of our risk estimates to those observed in cohort studies based on blood pressure measurements suggests that this source of bias was relatively minor.
Our study is also limited by the low response rate among controls, which is typical of recent population-based case-control studies. The use of sample weights helps to reduce the potential for bias arising from nonresponse, as the weights account for differential nonresponse across subgroups defined by factors (such as age, sex, and county of residence) for which data were available for both respondents and nonrespondents. That the hypertension history reported by our controls was comparable to that of NHANES suggests that selection bias was likely minimal.
Finally, comprehensive consideration of the interplay among race, hypertension, and renal cancer requires longitudinal information about blood pressure, anti-hypertensive medication use, weight and other potential confounders of the race-hypertension, hypertension-renal cancer, and race-renal cancer associations.35
Collection of data at this level of detail was not feasible in this population-based case-control study.
In conclusion, our study shows that hypertension is a risk factor for renal cancer among both blacks and whites. The stronger association observed among blacks using our crude definition of hypertension justifies more detailed assessment of hypertension in future studies. Reduction in risk of renal cancer may be a potential benefit of hypertension control, in addition to the known effects on heart disease and stroke, particularly in the black community.