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Gallbladder Cancer in the World: Epidemiology, Incidence, Mortality and Risk Factors

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Gallbladder Cancer in the World: Epidemiology, Incidence, Mortality and Risk Factors WCRJ 2018; 5 (3): e1124 GALLBLADDER CANCER IN THE WORLD: EPIDEMIOLOGY, INCIDENCE, MORTALITY AND RISK FACTORS N. MAHDAVIFAR1, M. MOHAMMADIAN1, H. SALEHINIYA2,3 1Department of Epidemiology and Biostatistics, Health Promotion Research Center, School of Public Health, Zahedan University of Medical Sciences, Zahedan, Iran 2Zabol University of Medical Sciences, Zabol, Iran 3Epidemiology and Biostatistics Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Abstract – Objective: Gallbladder cancer is a highly lethal malignancy with a poor prognosis. It is the sixth digestive tract cancer and one of the most common cancers in biliary ducts. The aim of this study was to investigate the incidence, mortality, and risk factors for gallbladder cancer in the world. Materials and Methods: This review study was conducted on published English studies by Jan- uary 2017 through a search of PubMed, Scopus and web of science databases. The search strategy included key words “gallbladder cancer”, “epidemiology”, “incidence”, “mortality”, “risk factors”, “world”. Studies related to incidence, mortality, and causes of gallbladder cancers were also stud- ied and included. Results: The five countries with the highest incidence of kidney cancer were Chile, Bolivia, Korea, Republic of, Lao PDR and Japan. The standard incidence of gallbladder cancer in the world was 2.2 per 100000. The five countries with the highest death rates were Chile, Bolivia, Korea, Republic of, Lao PDR and Nepal. The standardized death rate for gallbladder in the world was 1.7 per 100000 people. The most important risk factors for the cancer include gallstones, porcelain gallbladder, gallbladder polyps, bacterial and salmonella infections, chronic inflammation. Fruit and vegetable consumption are known as a protective agent for this cancer. Conclusions: The incidence of gallbladder cancer worldwide has a geographic variable pattern. Generally, knowledge of the stage of the disease at the time of diagnosis has a significant effect on the treatment of gallbladder cancer. It is also necessary to consider the risk factors to reduce this cancer. KEYWORDS: Gallbladder cancer, Epidemiology, Incidence, Mortality and risk factor. INTRODUCTION worldwide5,6. The incidence of gallbladder cancer worldwide has a geographic variable pattern; the Cancer is one of the major causes of mortality highest incidence has been reported in India, Asia, in human societies1,2. One of these cancers is Europe, and South America3,6. Gallbladder cancer gallbladder cancer, a very lethal malignancy with is more in women and biliary cancers more in poor prognosis3,4. This cancer is the sixth gastroin- males7. Due to the anatomical position of the gall- testinal tract cancer and one of the most common bladder and the non-specificity of the symptoms, biliary cancers. Among various cancers of the diagnosis of gallbladder cancers often occurs in gastrointestinal tract, it has a variety of incidence, late stages with a poor prognosis of less than 10% with an annual rate of 2.2 per 100000 people so that 5-year survival in many studies is less than Corresponding Author: Hamid Salehiniya, PhD Candidate; e-mail: [email protected] 1 5%8,9. Nearly from every five patients with cancer, NUMBER AND MORTALITY RATE four at diagnosis have advanced localized disease or metastases10. Given the importance of inform- In the whole world, in 2012, there were 142823 deaths ing about the incidence, mortality and risk factors from Gallbladder [(60339 were males and 82484 fe- in prevention programs, the aim of this study was males (Sex Ratio = 0.73)]. The standardized death rate to investigate the incidence, mortality, and risk for gallbladder in the world was 1.7 per 100000. The factors for gallbladder cancer in the world. standardized mortality rate for the cancer is 1.5 and 1.6 per 100000 per year in males, and 1.4 and 2.0 per 100000 per year in women in developed and non-de- METHODS veloped regions11. The five countries that had the highest standardized death rates for gallbladder were This review study was conducted on published En- Chile 7.8 per 100000, Bolivia with 7.5 per 100000, glish studies by January 2017 through a search of Korea, Republic with 4.8 per 100000, Lao PDR with PubMed, Scopus and web of science databases. The 4.7 per 100000 and Nepal 4.1 per 10000012,13,18. The search strategy included key words “gallbladder highest mortality rates in both sexes were in Latin cancer”, “epidemiology”, “incidence”, “mortality”, America, East Asia, and Eastern Europe. In the recent “risk factors”, “world”. Studies related to incidence, epidemiological report in the world, the highest death mortality, and causes of gallbladder cancers were and mortality rate of cancer has been in Chile and the studied and included. main cause of death from cancer in women19,20. The mortality of gallbladder cancers with the diagnosis of the disease is related to stage 0 to stage IV. A 5-year NUMBER AND INCIDENCE survival of this cancer varies from 60% to 1% for stage 0 to stage IV of the cancer3. The highest mortal- In 2012, there were 178101 cases of gallbladder ity rate is for patients diagnosed in stage III21. Deaths cancer worldwide (76844 cases were male and in some countries, such as the United States, Canada, 101,257 cases female (Sex Ratio = 0.75). The stan- Australia, and parts of Europe (Britain and Hungary), dardized incidence rate of the cancer was 2.2 per are declining, but are increasing in some areas, includ- 100000. The age standardized incidence rate of the ing Chile and Japan17. From an epidemiological point cancer was 2.3, 2.0 per 100000 people in men and of view, the incidence of the cancer is close to that of 2.0,2.4 per 100000 people in women in developed mortality. Countries with the highest incidence have and developing countries, respectively11. The five the highest mortality rates. Lack of access to health countries with the highest standardized incidence care in some parts of the world will help to increase of gallbladder cancer were Chile (9.7 per 100000), in these rates15. Bolivia (8.1 per 100000 people), Korea, Republic (6.5 per 100000), Lao PDR 4.8 per 100000 people and Japan 4.7 per 10000012,13. The incidence of gall- RISK FACTORS FOR GALLBLADDER bladder cancer in recent years has been rising in the CANCER advanced stage due to the time of diagnosis, often not curable. Despite the progress of information and The most important risk factors for gallbladder diagnostic techniques, the disease remains deadly8. cancers are summarized in Table 1. The factors are The incidence of this disease increases with age, as follows. and women are 2 to 6 times more likely to be at risk than men14. The incidence and mortality of this cancer are widespread in different geographical CHOLELITHIASIS regions, and in different ethnic groups and ethnic groups. It is due to differences in risk factors as- Many researches22-25 show that cholelithiasis is con- sociated with the development of gallbladder can- sidered a major risk factor for gallbladder cancer. cer and clinical manifestations during diagnosis in This clinical relevance is observed in patients with different areas12,14,15. The incidence of gallbladder symptomatic cholelithiasis, at least 20 years before cancer is high in many parts of the world, includ- the diagnosis of is gallbladder cancer described24,26. ing Chile, Peru, Bolivia, Korea, Japan, the Czech Based on studies, cholelithiasis was found in 70 to Republic, Slovakia, Spain and India6. The basis for 94% of patients with gallbladder cancer6,17. Although the difference is the difference in the distribution cholelithiasis is the cause of approximately 80% to of risk factors, such as living environment, genetic 90% of kidney cancer cases in the Western world. predisposition, diet, fertility, age and gender differ- It does not seem that the association between the ences (women are four to seven times more at risk incidence of gallstone cancer is strong with a par- than men)16,17. ticular type of stones27. Cholelithiasis constitutes a 2 GALLBLADDER CANCER IN THE WORLD: EPIDEMIOLOGY, INCIDENCE, MORTALITY AND RISK FACTORS TABLE 1. Risk factors for gallbladder cancer CHRONIC INFLAMMATION Strength of association Risk factors Chronic inflammation may have different causes, in- Cholelithiasis Strong cluding: mechanical obstruction through cholelithia- Bacterial and Salmonella Strong sis, environmental infections, polyps and adenomas, infections Porcelain gallbladder Strong self-immune patients and also anatomical changes Gallbladder polyps Strong such as pancreatobiliary. Studies show each of these Anomalous pancreatobiliary Moderate to strong as a contributing factor to the development of gall- duct junction bladder cancers38-40. The precise role of inflammation Endogenous and exogenous Moderate to strong in molecular progression of the development of gall- estrogens 31 Industrial exposure Moderate to strong bladder cancers has been shown to weaken . to carcinogens Pregnancy Moderate Familial tendency Moderate GALLBLADDER POLYPS AND Segmental adenomyomatosis Weak to moderate PORCELAIN GALLBLADDER of gallbladder Chronic inflammation Weak to moderate Polyposis coli Weak to moderate Gallbladder and gallbladder polyps are risk factors Mirizzi syndrome Weak to moderate for gallbladder cancer. Porcelain gallbladder and Obesity Weak to moderate gallbladder polyps are present in 12.5% to 62% of Protective factor: vegetables, patients with gallbladder cancer41,42. Cunningham et fruits fiber, vitamin intake al43 suggest that physicians should consider ethnicity major health problem in developed societies, which when patients are likely to have porcelain gallblad- affects 10 to 15 percent of the adult population. That der43. Several studies have reported the association means 20 to 25 million Americans have (or will between gallbladder polyps and the risk of gallblad- have) cholelithiasis28-30. Increasing the number and der cancer. Also, approximately 45% and 67% of pol- size of cholelithiasis in patients with gallbladder yps larger than 10 and 15 mm lead to malignancy44-47.
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