Abstract

Simple SummaryGallstones affect women more frequently than men. Symptomatic gallstones are treated with surgical removal of the gallbladder. Overweight, obesity, and exposure to female hormones can cause gallstones and also breast, uterine, and ovarian cancer. We assessed if surgical removal of the gallbladder is associated with these cancers in women. We found risk of ovarian cancer is increased within the first 6 months after surgery. Women undergoing this operation also show an increased risk of breast and uterine cancer up to 30 years after surgery. It is important to screen women with this surgery indication for the three abovementioned cancers.Background: Gallstones affect women more frequently than men, and symptomatic gallstones are increasingly treated with surgical removal of the gallbladder (cholecystectomy). Breast, endometrial, and ovarian cancer share several risk factors with gallstones, including overweight, obesity, and exposure to female sex hormones. We intended to assess the association between cholecystectomy and female cancer risk, which has not been comprehensively investigated. Methods: We investigated the risk of female cancers after cholecystectomy leveraging the Swedish Cancer, Population, Patient, and Death registries. Standardized incidence ratios (SIRs) adjusted for age, calendar period, socioeconomic status, and residential area were used to compare cancer risk in cholecystectomized and non-cholecystectomized women. Results: During a median follow-up of 11 years, 325,106 cholecystectomized women developed 10,431 primary breast, 2888 endometrial, 1577 ovarian, and 705 cervical cancers. The risk of ovarian cancer was increased by 35% (95% confidence interval (CI) 2% to 77%) in the first 6 months after cholecystectomy. The exclusion of cancers diagnosed in the first 6 months still resulted in an increased risk of endometrial (19%, 95%CI 14% to 23%) and breast (5%, 95%CI 3% to 7%) cancer, especially in women cholecystectomized after age 50 years. By contrast, cholecystectomized women showed decreased risks of cervical (−13%, 95%CI −20% to −7%) and ovarian (−6%, 95%CI −10% to −1%) cancer. Conclusions: The risk of ovarian cancer increased by 35% in a just short period of time (6 months) following the surgery. Therefore, it is worth ruling out ovarian cancer before cholecystectomy. Women undergoing cholecystectomy showed an increased risk of breast and endometrial cancer up to 30 years after surgery. Further evaluation of the association between gallstones or gallbladder removal on female cancer risk would allow for the assessment of the need to intensify cancer screening in cholecystectomized women.

Highlights

  • Surgical removal of the gallbladder is indicated mainly for the treatment of symptomatic gallstones and its complications

  • Considering any time elapsed since gallbladder removal, cholecystectomized women showed an increased risk of endometrial (18%, 95% CI 14% to 23%) and breast cancer (4%, 95% CI 2% to 6%; Table 1, column “All”)

  • In those with both a history of cholecystectomy and a diagnosis of gynecological cancers, the proportion of cholecystectomies performed after the cancer diagnoses in our dataset was 29.9% for breast cancer, 62.7% for cervical cancer, 33.1% for endometrial cancer, and 32.3% after ovarian cancer

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Summary

Introduction

Surgical removal of the gallbladder (cholecystectomy) is indicated mainly for the treatment of symptomatic gallstones (cholelithiasis) and its complications. Hormone replacement therapy in postmenopausal women and the use of oral contraceptives are associated with an increased risk of cholelithiasis [7–9]. Both obesity and rapid weight loss are established risk factors for gallstone formation [10–12]. Endometrial, and ovarian cancer share several risk factors with gallstones, including overweight, obesity, and exposure to female sex hormones. Results: During a median follow-up of 11 years, 325,106 cholecystectomized women developed 10,431 primary breast, 2888 endometrial, 1577 ovarian, and 705 cervical cancers. The exclusion of cancers diagnosed in the first 6 months still resulted in an increased risk of endometrial (19%, 95%CI 14% to 23%) and breast (5%, 95%CI 3% to 7%) cancer, especially in women cholecystectomized after age 50 years. By contrast, cholecystectomized women showed decreased risks of cervical

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