International renal‐cell cancer study. VIII. Role of diuretics, other anti‐hypertensive medications and hypertension

Abstract

Risk of renal-cell cancer in relation to use of diuretics, other anti-hypertensive medications and hypertension was assessed in a multi-center, population-based, case-control study conducted in Australia, Denmark, Germany, Sweden and the United States, using a shared protocol and questionnaire. A total of 1,732 histologically confirmed cases and 2,309 controls, frequency-matched to cases by age and sex, were interviewed. The association between renal-cell cancer and the drugs was estimated by relative risks (RRs) and 95% confidence intervals (CIs). Risks were increased among users of diuretics and other anti-hypertensive medications. After adjustment for hypertension, risk for diuretics was reduced to unity, except among long-term (15+ years) users. Risk for use of non-diuretic anti-hypertensive drugs remained significantly elevated and increased further with duration of use. Overall risk was not enhanced when both classes of medications were used. Excess risk was not restricted to any specific type of diuretic or anti-hypertensive drug and no trend was observed with estimated lifetime consumption of any particular type of product. The RR for hypertension after adjustment for diuretics and other anti-hypertensive medications was 1.4 (95% CI = 1.2-1.7), although among non-users of any anti-hypertensive medications, there was little excess risk associated with a history of hypertension. Exclusion of drug use that first occurred within 5 years of cancer diagnosis or interview did not alter the associations. Our findings suggest small effects on renal-cell cancer risk associated with hypertension and use of diuretics and other anti-hypertensive medications. However, because of potential misclassifications of these highly correlated variables, it is difficult to distinguish the effect of treatment from its indication, hypertension.

A cohort study of antihypertensive treatments and risk of renal cell cancer

“…Only one case of RCC was diagnosed among users of potassium-sparing agents. Based on past studies in this population and others, it is unlikely that calcium antagonists or beta blockers, or ACE inhibitors are associated with cancer (McLaughlin et al, 1995;Olsen et al, 1997;McLaughlin and Lipworth, 2000;Sorensen et al, 2000;Friis et al, 2001;Grossman et al, 2001). To our knowledge this is the first study to examine the relation between angiotensin II antagonists and RCC.…”

“…Thus, failure to adjust for confounding by pre-existing hypertension in our study may have generated inflated risk estimates. When adjustment for high blood pressure is performed, it appears to eliminate the excess risk associated with diuretic use (McLaughlin et al, 1995). We examined the specific classes of diuretics and found similar risks across all groups.…”

“…Several large-scale population-based case -control and cohort studies which adjusted for use of diuretics and other AHT have reported elevated relative risks for RCC associated with hypertension, independent of use of AHT (McLaughlin et al, 1995;Yuan et al, 1998;Chow et al, 2000;McLaughlin and Lipworth, 2000). In contrast, adjustment for high blood pressure appears to eliminate any excess risk for RCC associated with AHT use (McLaughlin et al, 1995;Yuan et al, 1998;Shapiro et al, 1999;McLaughlin and Lipworth, 2000). In an attempt to control for potential confounding variables, we compared beta blockers and other medications and found that all of the risk estimates were close to expectation.…”

“…Concerns have been raised that certain AHT may increase the risk of renal cell carcinoma (RCC) whether by being directly carcinogenic, by eliciting or accelerating other carcinogens, or by impairing defence mechanisms (Yu et al, 1986;McLaughlin et al, 1995;Grossman et al, 2001).…”

Blood pressure and renal cancer risk: the HUNT Study in Norway

“…In men, there was no association with blood pressure. The association of blood pressure with risk of renal cell cancer has been investigated in a number of cohort (Fraser et al, 1990;Grove et al, 1991;Coughlin et al, 1997;Heath et al, 1997;Chow et al, 2000;Choi et al, 2005;Flaherty et al, 2005;Fryzek et al, 2005;Lindgren et al, 2005;Schouten et al, 2005) and case -control (McLaughlin et al, 1995;Yuan et al, 1998;Shapiro et al, 1999) studies, using as principal exposure variable either recorded blood pressure or reported hypertension. In men, recorded blood pressure has shown a convincing exposure -response gradient related to renal cell cancer risk (Coughlin et al, 1997;Chow et al, 2000).…”