How does obesity contribute to the risk of gallbladder cancer in females?

1.

Elsevier ClinicalKey Clinical Overview

Diagnosis Anomalous junction of the pancreaticobiliary ductal system Causes reflux of pancreatic fluid proximally into biliary tree Associated with onset of gallbladder cancer at a young age 10% to 15% of patients of Asian ancestry will develop gallbladder cancer in the presence of this anomaly Gallbladder calcification Older literature describes up to 60% incidence of gallbladder cancer among patients with diffuse calcification pattern known as porcelain gallbladder More recent literature describes only weak association, with an incidence of 2% to 3% Inflammation induced by chronic carriage of Salmonella typhi may increase risk Environmental risk factors Occupational exposure to chemicals in a variety of industries Petroleum refining Textile industry Paper milling Rubber industry Shoemaking Cigarette smoking Aflatoxin exposure may increase risk, but more research is needed to verify the association Comorbidities associated with increased risk Primary sclerosing cholangitis Lifetime risk of approximately 2% Screen annually for all biliary tract malignancies, including gallbladder cancer, using transabdominal ultrasonography; some centers use magnetic resonance cholangiopancreatography combined with contrast-enhanced MRI of the liver Obesity Relative risk of 1.66 (stronger association in females) Female reproductive factors associated with increased risk Increasing parity and higher number of reproductive years Menopausal hormone therapy with combination of estrogen and progesterone More than 2-fold increase in risk of gallbladder cancer with orally administered formulations Transdermal preparations are associated with a lower risk compared with oral formulations No increase in risk with estrogen-only preparations, topical creams and suppositories, and these are associated with lower risk of extrahepatic cholangiocarcinoma Regional variation in risk Risk varies by region; in general, higher incidence in developing countries

Synopsis Usually diagnosed in late, incurable stage; a high index of suspicion is required for diagnosis Most commonly encountered risk factors for gallbladder cancer are presence of gallstones, female sex, and obesity—all of which overlap with risk factors for benign gallbladder disease It is often unclear if symptoms of gallbladder cancer are superimposed on those of benign gallstone-related disease or if symptoms are mostly related to presence of gallstones with silent malignancy When evaluating a patient for cholecystectomy for presumed benign biliary disease, the presence of known risk factors increases the index of suspicion for the possibility of gallbladder cancer (eg, high-risk ethnicity or geographic area of residence, anomalous junction of pancreaticobiliary ductal system, gallbladder polyp on imaging, chronic typhoid carrier status, comorbid primary sclerosing cholangitis)

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Tamimi, Rulla M. (2024). In Goldman-Cecil Medicine (pp. 1243). DOI: 10.1016/B978-0-323-93038-3.00165-9

Consistent evidence links excess body weight (Chapter 201) with the risk of cancer at multiple sites. The risk is strongest (a three-fold increase in risk) for endometrial and esophageal cancers and more modest (relative risks of 1.5 to 3.0) for cancers of the kidney, liver, pancreas, and stomach, as well as for multiple myeloma and meningioma. The lowest relative risks (1.0 to 1.5) are for colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers. The biologic mechanisms that have been proposed to underlie these associations include chronic inflammation, hyperinsulinemia/insulin resistance, insulin-like growth factor (IGF)-1 pathways, and the impact of obesity on circulating sex steroids. Given the strong association between adiposity and many cancers, maintaining a healthy body weight is an important recommendation for cancer prevention. For example, the marked weight loss after bariatric surgery is associated with a significant reduction in the incidence of cancer. Strong evidence links certain cancers with adult height independent of obesity. For example, adult height is positively associated with the risks of colorectal, ovarian, and breast cancer.In a nationwide study in Sweden, every 10cm increase in height was associated with about a 20% increased risk of cancer in women and about a 10% increased risk of cancer in men.All cancer sites showed a positive association, with the strongest relative risk (35 to 40%) for malignant melanoma. Height may reflect a larger number of cells at risk of transformation, or adult height may reflect energy intake or exposures to growth factors early in life. For example, levels of IGF-1 in childhood are strongly correlated with height.

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Jensen, Michael D., Bessesen, Daniel H. (2024). In Goldman-Cecil Medicine (pp. 1463). DOI: 10.1016/B978-0-323-93038-3.00201-X

The excess body weight associated with obesity is thought to be responsible for the increased prevalence of lower extremity degenerative joint disease (Chapter 241). Severely obese individuals may also have problems with venous stasis (Chapter 68), which is occasionally aggravated by right-sided heart failure. Sleep apnea (Chapter 374) is common in severely obese patients and is more prevalent in men and in women with an upper body/visceral obesity. Sleep apnea is most likely explained by enlargement of upper airway soft tissue, resulting in collapse of the upper airways during inspiration while sleeping. The obstruction leads to apneas, with hypoxemia, hypercarbia, and high levels of catecholamines and endothelins. The frequent arousals to restore breathing result in poor sleep quality. Sleep apnea is associated with an increased risk of hypertension, and if sleep apnea is severe, it can lead to right-sided heart failure and sudden death. Obesity is associated with an increased risk of at least 13 different types of cancer (breast, esophageal, liver, gallbladder, stomach, pancreas, colorectal, ovarian, uterine, renal cell, thyroid, meningioma, and multiple myeloma),likely due to higher levels of insulin-like growth factor and estrogens. Obese individuals have a greater prevalence of gastroesophageal reflux disease (Chapter 124) and gallstones (Chapter 141). Fatty liver and nonalcoholic steatohepatitis (Chapter 138) are strongly associated with overweight, obesity, and the metabolic syndrome.

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Pati S, Irfan W, Jameel A, Ahmed S, Shahid RK. Cancers. 2023;15(2):485. doi:10.3390/cancers15020485. Copyright License: CC BY

Publish date: January 4, 2023.

BACKGROUND: Obesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity. METHODS: A literature search using PubMed and Google Scholar was performed and the keywords 'obesity' and cancer' were used. The search was limited to research papers published in English prior to September 2022 and focused on studies that investigated epidemiology, the pathogenesis of cancer, cancer incidence and the risk of recurrence, and the management of obesity. RESULTS: About 4-8% of all cancers are attributed to obesity. Obesity is a risk factor for several major cancers, including post-menopausal breast, colorectal, endometrial, kidney, esophageal, pancreatic, liver, and gallbladder cancer. Excess body fat results in an approximately 17% increased risk of cancer-specific mortality. The relationship between obesity and the risk associated with the development of cancer and its recurrence is not fully understood and involves altered fatty acid metabolism, extracellular matrix remodeling, the secretion of adipokines and anabolic and sex hormones, immune dysregulation, and chronic inflammation. Obesity may also increase treatment-related adverse effects and influence treatment decisions regarding specific types of cancer therapy. Structured exercise in combination with dietary support and behavior therapy are effective interventions. Treatment with glucagon-like peptide-1 analogues and bariatric surgery result in more rapid weight loss and can be considered in selected cancer survivors. CONCLUSIONS: Obesity increases cancer risk and mortality.

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Elsevier ClinicalKey Clinical Overview

Diagnosis Subsubsection Title: Age: No evidence of association with age; however, the risk for developing cholelithiasis is highest between ages 55 and 62 years Subsubsection Title: Sex: No evidence of association with sex; however, incidence of cholelithiasis is twice as high in females in any age group Subsubsection Title: Other risk factors/associations: Obesity, as well as rapid weight loss resulting from bariatric surgery, is associated with increased risk of cholelithiasis and cholecystitis Certain medications, including the following, may indirectly increase the risk of cholecystitis by promoting gallstone formation: Ampicillin Anticholinergic agents Ceftriaxone Dapsone Erythromycin Fibrates Hormone replacement therapy Octreotide Glucagon-like peptide-1 receptor agonists Statins may reduce the risk of cholecystectomy for gallstones Risk factors for the development of acute acalculous cholecystitis include: Sepsis (eg, bacterial, fungal, parasitic, viral) Shock Burns Prolonged fasting Trauma leading to hospitalization Critical illness (any patient requiring ICU care)