Renal cell carcinoma and thiazide use: a historical, case-control study (California, USA)

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Abstract
Renal cell carcinoma has been linked to hypertension and antihypertensive medications. We investigated the association between renal cell carcinoma and the use of thiazide in a case-control study of 167 men and 90 women. Subjects were members of the Kaiser Permanente Medical Care Program in northern California (United States) who had taken a multiphasic health check-up from 1964 through 1988 and who were evaluated for cancer until the end of 1989. Control subjects received the same check-up, were matched by gender, year of check-up, and age at check-up, and had to be in the health plan until the date on which renal cell carcinoma was diagnosed. Data on known and potential risk factors, including hypertension, body mass index (BMI), and smoking status, were collected from the record of the check-up. Thiazide use was abstracted from the medical chart, which was reviewed from the date of the first entry until the date on which the cancer was diagnosed or the equivalent date for control subjects. The mean follow-back to check-up was 11.3 years. Among women, we found a significantly elevated risk of 4.0 (95 percent confidence interval [CI] 1.5–10.8) associated with ever having used thiazide after we adjusted for smoking, BMI, hypertension, and history of kidney infection at check-up. We did not find a statistically significantly elevated risk in men. Smoking was related to renal cell carcinoma in men (odds ratio [OR] 2.5, CI=1.1–5.4) for those who smoked at least one pack per day compared with those who had never smoked, but was not related in women. We found a statistically nonsignificant relation between BMI and renal cell carcinoma. After we adjusted for thiazide use, we did not find that hypertension was a statistically significant risk factor for renal cell carcinoma. Analysis of the dosage of thiazide measured by time since first use, duration of use, number of mentions of use in the chart, and an estimate of total grams of exposure did not result in any convincing dose-response relation. These findings are consistent with a growing body of data linking antihypertensive medication with renal cell carcinoma. We are unable to conclude whether thiazide use or some other characteristic of hypertensive persons taking these medications is responsible for the association.