Dataset Information

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk.

ABSTRACT: Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery-induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III-IV obesity (body mass index ?40 and ?50 kg/m² , respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months' follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki-67), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy-two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was -32.7 and -62.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of AH resolved (5/6) without intervention (3/6) or with intrauterine progestin (2/6). Biomarkers of endometrial proliferation (Ki-67), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA-IR) and inflammation (hsCRP, IL-6), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down-regulation of PI3K-AKT-mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease.

SUBMITTER: MacKintosh ML

PROVIDER: S-EPMC6519061 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk.

MacKintosh Michelle L ML Derbyshire Abigail E AE McVey Rhona J RJ Bolton James J Nickkho-Amiry Mahshid M Higgins Catherine L CL Kamieniorz Martyna M Pemberton Philip W PW Kirmani Bilal H BH Ahmed Babur B Syed Akheel A AA Ammori Basil J BJ Renehan Andrew G AG Kitchener Henry C HC Crosbie Emma J EJ

International journal of cancer 20181120 3

Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery-induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III-IV obesity (body mass index ≥40 and ≥50 kg/m<sup>2</sup> , respectively) immediately prior to gastric bypass or sleeve gastrectomy, ...[more]

PMID: 30289975

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Project description:ImportanceAlthough bariatric surgery is effective against morbid obesity, the association of this surgery with the risk of colorectal cancer remains controversial.ObjectiveTo assess whether bariatric surgery is associated with altered risk of colorectal cancer among individuals with obesity.Design, setting, and participantsThis retrospective, population-based, multicenter, cohort study based on French electronic health data included 1 045 348 individuals with obesity, aged 50 to 75 years, and free of colorectal cancer at baseline. All inpatients with obesity having data recorded during a hospital stay between 2009 and 2018 by the French national health insurance information system database were followed up for a mean (SD) of 5.3 (2.1) years for those who did not undergo bariatric surgery and 5.7 (2.2) years for those who underwent bariatric surgery. Two groups of patients comparable in terms of age, sex, body mass index, follow-up, comorbidities, and conditions who did or did not undergo surgery were also obtained by propensity score matching.ExposuresBariatric surgery (n = 74 131), including adjustable gastric banding, sleeve gastrectomy, gastric bypass; or no bariatric surgery (n = 971 217).Main outcomes and measuresPrimary outcome was incident colorectal cancer. Standardized incidence ratios were calculated using age-, sex-, and calendar year-matched colorectal cancer incidence among the general French population during the corresponding years. Secondary outcome was incident colorectal benign polyps.ResultsAmong a total of 1 045 348 patients, the mean (SD) age was 57.3 (5.5) years for the 74 131 patients in the surgical cohort vs 63.4 (7.0) years for the 971 217 patients in the nonsurgical cohort. The mean (SD) follow-up was 6.2 (2.1) years for patients who underwent adjustable gastric banding, 5.5 (2.1) years for patients who underwent sleeve gastrectomy, and 5.7 (2.2) years for patients who underwent gastric bypass. In total, 13 052 incident colorectal cancers (1.2%) and 63 649 colorectal benign polyps were diagnosed. The rate of colorectal cancer was 0.6% in the bariatric surgery cohort and 1.3% in the cohort without bariatric surgery. In the latter cohort, 9417 cases were expected vs 12 629 observed, a standardized incidence ratio of 1.34 (95% CI, 1.32-1.36). In the bariatric surgery cohort, 428 cases were expected and 423 observed, a standardized incidence ratio of 1.0 (95% CI, 0.90-1.09). Propensity score-matched hazard ratios in comparable operated vs nonoperated groups were 0.68 (95% CI, 0.60-0.77) for colorectal cancer and 0.56 (95% CI, 0.53-0.59) for colorectal benign polyp. There were fewer new diagnoses of colorectal cancer after gastric bypass (123 of 22 343 [0.5%]) and sleeve gastrectomy (185 of 35 328 [0.5%]) than after adjustable gastric banding (115 of 16 460 [0.7%]), and more colorectal benign polyps after adjustable gastric banding (775 of 15 647 [5.0%]) than after gastric bypass (639 of 20 863 [3.1%]) or sleeve gastrectomy (1005 of 32 680 [3.1%]).Conclusion and relevanceThe results of this nationwide cohort study suggested that following bariatric surgery, patients with obesity share the same risk of colorectal cancer as the general population, whereas for patients with obesity who do not undergo bariatric surgery, the risk is 34% above that of the general population.

Project description:ImportanceExcess adiposity confers higher risk of breast cancer for women. For women who have lost substantial weight, it is unclear whether previous obesity confers residual increased baseline risk of breast cancer compared with peers without obesity.ObjectivesTo determine whether there is a residual risk of breast cancer due to prior obesity among patients who undergo bariatric surgery.Design, setting, and participantsRetrospective matched cohort study of 69 260 women with index date between January 1, 2010, and December 31, 2016. Patients were followed up for 5 years after bariatric surgery or index date. Population-based clinical and administrative data from multiple databases in Ontario, Canada, were used to match a cohort of women who underwent bariatric surgery for obesity (baseline body mass index [BMI] ≥35 with comorbid conditions or BMI ≥40) to women without a history of bariatric surgery according to age and breast cancer screening history. Nonsurgical controls were divided into 4 BMI categories (<25, 25-29, 30-34, and ≥35). Data were analyzed on October 21, 2021.ExposuresWeight loss via bariatric surgery.Main outcomes and measuresResidual hazard of breast cancer after washout periods of 1, 2, and 5 years. Comparisons were made between the surgical and nonsurgical cohorts overall and within each of the BMI subgroups.ResultsIn total, 69 260 women were included in the analysis, with 13 852 women in each of the 5 study cohorts. The mean (SD) age was 45.1 (10.9) years. In the postsurgical cohort vs the overall nonsurgical cohort (n = 55 408), there was an increased hazard for incident breast cancer in the nonsurgical group after washout periods of 1 year (hazard ratio [HR], 1.40 [95% CI, 1.18-1.67]), 2 years (HR, 1.31 [95% CI, 1.12-1.53]), and 5 years (HR, 1.38 [95% CI, 1.21-1.58]). When the postsurgical cohort was compared with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different regardless of the washout period, whereas there was a reduced hazard for incident breast cancer among postsurgical patients compared with nonsurgical patients in all high BMI categories (BMI ≥25).Conclusions and relevanceFindings suggest that bariatric surgery was associated with a reduced risk of developing breast cancer for women with prior obesity equivalent to that of a woman with a BMI less than 25 and a lower risk when compared with all groups with BMI greater than or equal to 25.

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The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk.

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The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk.

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