December 16, 2010 — Hysterectomy for reasons other than cancer is significantly related to renal cell carcinoma, according to a study published December 13 in the Archives of Internal Medicine.

The most frequently performed gynecologic procedure, hysterectomy is not cancer related in the majority of cases. Evidence suggests that the surgery may be linked to this most common type of kidney cancer, which occurs in the lining of the proximal convoluted tubule, making hysterectomy a preventable cause of the disease. However, substantiation is lacking.

"Hysterectomy for benign indications is associated with increased risk of renal cell carcinoma," write Daniel Altman, MD, PhD, from the Department of Medical Epidemiology and Biostatistics, at the Karolinska Institutet, in Stockholm, Sweden, and colleagues. "However, the evidence is mostly derived from hospital-based series or retrospective studies lacking control of the temporal aspects of the relationship; therefore, the suggested association is contentious."

Using data from 1973 to 2003, accumulated through a compilation of Swedish healthcare registries including the Classification of Operations and Major Procedures, Cancer, and Cause-of-Death registries, the investigators launched a population-based cohort study. The study involved 184,945 women who had undergone hysterectomy and 657,288 matched women with intact uteruses.

The researchers evaluated the risk for renal cell carcinoma from hysterectomy using Cox proportional hazards regression models.

Short- and Long-Term Risks Increase After Hysterectomy

The results showed that women who had undergone hysterectomy had a higher unadjusted rate of renal cell carcinoma vs those who had not had the surgery, as follows:

Among women who have had a hysterectomy, the crude incidence rates of renal cell carcinoma were 17.4 cases per 100,000 person-years; among those whose uteruses were not removed, the incidence was 13.1 cases per 100,000 person-years.
The overall adjusted hazards ratio (HRs) of women with hysterectomy vs those whose uteruses were not surgically removed corresponded to significantly increased risks for renal cell carcinoma (HR, 1.50; 95% confidence interval [CI], 1.33 - 1.69).
The women who were the youngest at the time of surgery (≤ 44 years) had the greatest risk (HR, 2.03; 95% CI, 1.55 - 2.67), which attenuated with increasing age.
In related findings, the adjusted overall elevated risk for bladder cancer after hysterectomy (HR, 1.21; 95% CI, 1.07 - 1.37) was of smaller significance, but that trend also increased with a decrease in the patients’ ages at surgery.
Regarding bladder cancer, the age variable was significant only during the 10 years after surgery, whereas for renal cell carcinoma, the positive association with younger age at surgery persisted for more than 20 years.

"Given current trends in gynecologic surgery whereby women are offered hysterectomy at younger ages, this has important implications and may influence future occurrence of renal cell carcinoma," the study authors write.

The investigators stated a limitation to their study. Obstetric history was unavailable before 1973, hampering the ability of the authors to interpret the long-term association between childbirth and renal cell carcinoma among women who were 52 years and older at the close of the follow-up period.

Future studies should probe more deeply into the categories related to greater risk.

"Further efforts are needed to identify groups of women at high risk of renal cell carcinoma in the aftermath of hysterectomy," the study authors write.