Ethnicity, genetic variants, risk factors and cholelithiasis: The need for eco-epidemiological studies and genomic analysis in Latin American surgery

Abstract

Dear Editor Cholelithiasis is one of the most frequent gastrointestinal pathologies treated with invasive management worldwide in gastroenterology, general surgery and gastrointestinal surgery [1]. The prevalence of this disease varies by region, with approximately 15% of the U.S. population reported to have gallstone disease [1], and 20% of patients with gallstone disease have symptoms and/or requiring complications for surgical treatment. The number of cholecystectomies remains high, ranging between 190,000 and 700,000 per year per country [1–3]. As there are numerous risk factors for development of gallstones, and gallstone disease is a potential risk factor for gallbladder cancer, identification of predictors for early and safe management of this condition is of current research interest in surgery [2]. In addition, in-hospital investigations, pharmacological management and readmission to emergency departments for moderate or severe symptoms carry high healthcare costs [3]. It has also been observed that ethnicity and genetic variants among populations substantially influence onset and evolution of this disease. A recently published study evaluated mitochondrial DNA expression, mitochondrial respiratory chain complex activity and cholesterol metabolism in a Chinese population using trans-mitochondrial technology showed that there was an elevated risk of developing gallstone disease in individuals with both personal and familial variants of mitochondrial DNA expression, mitochondrial respiratory chain complex activity and cholesterol metabolism (OR 4.5; CI 95%, 2.1–9.4, p = 0,0001) [4]. These authors found that these variations disrupted specific cellular and molecular pathways, modified cholesterol transport and increased risks of gallstone disease [4]. These types of variants have been little studied and the results of this study represented novel findings which are different from the results of studies coming from other regions of the world, leading to the conclusion that ethnicity and genetic variants are factors to be considered for the dynamics of development of gallstone disease. Eco-epidemiology is a field of epidemiology that combines social, molecular and population aspects for the study of community health [5]. In surgery, the available evidence on molecular and clinical characterization and correlation of surgical diseases is scarce, especially those evidence coming from low- and middle-income countries. Thus, the eco-epidemiology in surgery should be a transcendental line to take in controlling the heavy burden of certain surgical diseases in populations with risk factors, such as gallstone disease for the Latin American population. Figueiredo et al. [6] conducted in a prospective cohort study using a representative sample composing of different ethnicities. They found that female and Latino is a potential risk factor for cholelithiasis (p < 0.003) [6]. Parity, which is high even at early ages in Latin America, was also a risk factor. Similarly, the impacts of traditional risk factors including obesity, nutritional status, physical activity, smoking and red meat consumption were not the same in all studied the population groups, but the Latino group was one of the most affected [6]. On the other hand, Gu et al. [7] studied the risk factors for gallstone disease in a population in Shanghai. Unlike the study of Figueiredo et al. [6], by using multivariate logistic regression analyses, they showed that body weight and diet were not related to the incidences of gallstone, which was only 4.11%, out of 2288 patients on a follow-up of approximately 3 years [7]. Such findings corroborate the impact of ethnicity on behavior of the disease. However, published studies on genomic analysis in this disease found significant differences in results depending on the local context. Although genomic analysis is often used in microbiological analysis, it may also have other applicability including differences in gallbladder genetic behavior among different population groups [8,9]. Specifically, metagenomic studies have shown that bacteria play a fundamental role in development of gallstones and complications of cholelithiasis [8,9]. As gallbladder cancer is a complication that carries high health costs with a high mortality rate, eco-epidemiological studies and genomic analysis can allow a more rigorous weighing between whether there is a need to perform prophylactic cholecystectomy or to execute a less aggressive plan for gallbladder cancer [8–10]. As stated by Salazar et al. [10], molecular characterizations of gallstone disease could be the only way to predict behavior of this disease and its potential complications. In the order of priorities, it is necessary to strongly involve translational medicine in Latin American surgery, and to promote eco-epidemiological studies and genomic analysis in patients with risk factors for gallstone disease. It is also important to establish work teams to evaluate the natural history of the disease in certain population groups, determine evolution of the disease at in-hospital levels and evaluate final outcomes of these studies. The relevance on studies on this topic lies in the fact that low- and middle-income countries such as those in Latin America lack an adequate number of subspecialists in their total populations, so that specialists in general surgery have often to provide relevant data for this type of pathology, thus making it difficult to further improve on indicators for a disease burden [11–13]. A new objective for evolution of Latin American surgery is to allow the formation of research working groups of undergraduate students, residents, professors and other professionals related to the field as researchers in both basic and clinical sciences. Ethical approval It is not necessary. Sources of funding None. Author contribution All authors equally contributed to the analysis and writing of the manuscript. Research registration Unique Identifying number (UIN) 1. Name of the registry: Not applicable. 2. Unique Identifying number or registration ID: Not applicable. 3. Hyperlink to your specific registration (must be publicly accessible and will be checked): Not applicable. Guarantor Ivan David Lozada-Martinez, Grupo Prometheus y Biomedicina Aplicada a las Ciencias Clínicas, School of Medicine, Universidad de Cartagena, Cartagena, Colombia. Email: [email protected]. Provenance and peer review Not commissioned, internally peer-reviewed. Declaration of competing interest None.

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