Inflammation is an important physiological response of the organism to restore homeostasis upon pathogenic or damaging stimuli. However, the persistence of the harmful trigger or a deficient resolution of the process can evolve into a state of low-grade, chronic inflammation. This condition is strongly associated with the development of several increasingly prevalent and serious chronic conditions, such as obesity, cancer, and cardiovascular diseases, elevating overall morbidity and mortality worldwide. The current pandemic of chronic diseases underscores the need to address chronic inflammation, its pathogenic mechanisms, and potential preventive measures to limit its current widespread impact. The present review discusses the current knowledge and research gaps regarding the association between low-grade chronic inflammation and chronic diseases, focusing on obesity, cardiovascular diseases, digestive diseases, and cancer. We examine the state of the art in selected aspects of the topic and propose future directions and approaches for the field.

In Chile, where gallbladder cancer (GBC) rates are high and typhoid fever was endemic until the 1990s, we evaluated the association betweenSalmonella entericaserovar Typhi (S. Typhi) antibodies andGBC. We tested 39GBCcases, 40 gallstone controls, and 39 population‐based controls forS. Typhi Vi antibodies and performed culture and quantitative polymerase chain reaction for the subset with bile, gallstone, tissue, and stool samples available. We calculated gender and education‐adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association withGBC. We also conducted a meta‐analysis of >1000GBCcases by combining our results with previous studies.GBCcases were more likely to have high Vi antibody titer levels than combined controls (OR: 4.0, 95%CI: 0.9–18.3), althoughS. Typhi was not recovered from bile, gallstone, tissue, or stool samples. In our meta‐analysis, the summary relative risk was 4.6 (95%CI: 3.1–6.8,P_{heterogeneity}=0.6) for anti‐Vi and 5.0 (95%CI: 2.7–9.3,P_{heterogeneity} = 0.2) for bile or stool culture. Our results are consistent with the meta‐analysis. Despite differences in study methods (e.g.,S. Typhi detection assay), most studies found a positive association betweenS. Typhi andGBC. However, the mechanism underlying this association requires further investigation

In Chile, gallbladder cancer is a leading cause of cancer death in women. Other than gallstones, gallbladder cancer etiology remains largely unclear. Exposure to aflatoxin, a liver carcinogen, is associated with bile duct epithelium proliferation in both animals and humans,¹ and with gallbladder cancer in primates.¹ Aflatoxin contamination has been identified in Chile, including in ají rojo (red chili peppers). Ají rojo is associated with gallbladder cancer²; however, the association of aflatoxin with gallbladder cancer in humans has not been directly evaluated.

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10⁻²⁷). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data. A lot of attention has been paid to Latino heterogeneity related to individual proportions of Native American, European and African ancestry. The importance of the type of Native American ancestry for health, however, has hardly been studied. Here we examined genetic data from 2,039 admixed Chileans to investigate possible associations between top causes of death and the two major types of Native American ancestry in Chile. Our findings demonstrate the necessity of suitable surrogates for ancestry estimation which mirror the actual composition of the study population, and the advantage of considering fine-scale Latino heterogeneity for unraveling of disease etiology and personalized healthcare.

Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant both for etiologic understanding and for clinical purposes. Data on the frequency and distribution of gallbladder dysplasia are lacking owing to limited gallbladder sampling and inability to visualize dysplasia grossly. An expert pathology group used consensus criteria to review 140 totally sampled consecutive cholecystectomy specimens from Chilean women. Three cases (2%) revealed incidental invasive carcinoma, all T2, along with high-grade dysplasia (HGD). The surface areas covered by dysplasia or cancer in these cases were 9%, 37%, and 87%. Although the first longitudinal ("diagnostic") section of the whole gallbladder captured HGD or cancer in all 3 cases, the deepest focus of invasive carcinoma was not present in this section. Fourteen additional cases (10%) had low-grade dysplasia (LGD), which was typically very focal (covering <5% of the surface) and most often occurred in the fundus. LGD was not present in the diagnostic section of 5 cases (38%) and would have been missed without additional sampling. None of the cancers or dysplasias were grossly visible. Although HGD and carcinoma are likely to be identified in "diagnostic" sections, accurate staging requires total sampling. LGD is typically very focal and would often be missed in routine practice. To identify cancer precursors, additional sampling, particularly of the fundus, may be warranted. The predominance of LGD in the fundus also provides etiologic insight, supporting the contribution of gallstones and chronic inflammation.