Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease (particularly nonalcoholic fatty liver disease) and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. HCC surveillance and early detection increase the chance of potentially curative treatment; however, HCC surveillance is substantially underutilized, even in countries with sufficient medical resources. Early-stage HCC can be treated curatively by local ablation, surgical resection or liver transplantation. Treatment selection depends on tumour characteristics, the severity of underlying liver dysfunction, age, other medical comorbidities, and available medical resources and local expertise. Catheter-based locoregional treatment is used in patients with intermediate-stage cancer. Kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC. Together, rational deployment of prevention, attainment of global goals for viral hepatitis eradication, and improvements in HCC surveillance and therapy hold promise for achieving a substantial reduction in the worldwide HCC burden within the next few decades.
The association of overweight and obesity with premenopausal breast cancer remained unclear, ethnicity could play a role. A MEDLINE and PUBMED search of all studies on obesity and premenopausal breast cancer published from 2000 to 2010 was conducted. Dose-response meta-analysis was used to determine the risk of premenopausal breast cancer associated with different anthropometric measurements in different ethnic groups. For body mass index (BMI), each 5 kg m(-2) increase was inversely associated with the risk of premenopausal breast cancer (RR = 0.95, 95% confidence interval [CI]: 0.94, 0.97). After stratification by ethnicity, the inverse association remained significant only among Africans (RR = 0.95, 95% CI: 0.91, 0.98) and Caucasians (RR = 0.93, 95% CI: 0.91, 0.95). In contrast, among Asian women, a significant positive association was observed. For waist-to-hip ratio (WHR), each 0.1 unit increase was positively associated with premenopausal breast cancer (RR = 1.08, 95% CI: 1.01, 1.16); the largest effect was detected in Asian women (RR = 1.19, 95% CI: 1.15, 1.24), while small effects of 5% and 6% were observed in African and Caucasian women, respectively. Our results suggest the importance of considering both fat distribution and ethnicity when studying premenopausal breast cancer.
Germline pathogenic variants in TP53 gene have different consequences according to cell, tissue, context and age. The occurrence of frequent variants in patients with no criteria suggestive of LFS calls for attention in predicting individual risk and highlights the need of additional predictors for assigning carriers to appropriate surveillance programs.
An estimated 1.38 million new cases of breast cancer (BC) are diagnosed each year in women worldwide. Of these, the majority are categorized as invasive ductal cell carcinoma. Subgroups of BC are frequently distinguished into five “intrinsic” subtypes, namely, luminal A, luminal B, normal-like, HER2-positive, and basal-like subtypes. Epidemiological evidence has shown that anthropometric factors are implicated in BC development. Overall consistent positive associations have been observed between high body mass index (BMI) and waist-to-hip ratio (WHR) and the risk of BC among postmenopausal women, while conflicting results persist for premenopausal BC, both for BMI and for other anthropometric parameters as well as across ethnic groups. Furthermore, some evidence suggests that body size, body shape, and weight gain during childhood or adolescence may play a role in the risk of BC. In this paper, we describe the evidence linking anthropometric indices at different ages and BC risk, in order to improve our understanding of the role of body fat distribution in the risk of BC, investigate differences in these associations according to menopausal status and ethnic groups, and discuss the potential biological mechanisms linking body size and BC risk.
We have performed a meta-analysis of cancer risk associated with the rs17878362 polymorphism of the TP53 suppressor gene (PIN3, (polymorphism in intron 3), 16 bp sequence insertion/duplication in intron 3), using a compilation of a total of 25 published studies with 10 786 cases and 11 760 controls. Homozygote carriers of the duplicated allele (A2A2) had a significantly increased cancer risk compared with A1A1 carriers (aggregated odds ratio (OR)=1.45, 95% confidence interval (CI)=1.22–1.74). However, there was no significant effect for the A1A2 heterozygotes (A1A2 versus A1A1 aggregated OR=1.08, 95% CI=0.99–1.18). No significant heterogeneity or publication bias was detected in the data set analysed. When comparing populations groups, increased cancer risk was associated with A2A2 carriage in Indian, Mediterranean and Northern Europe populations but not in the Caucasian population of the United States. Analysis by cancer site showed an increased risk for A2A2 carriers for breast and colorectal, but not for lung cancers. These results support that the A2A2 genotype of rs17878362 is associated with increased cancer risk, with population and tumour-specific effects.
Reports of variable cancer penetrance in Li-Fraumeni syndrome (LFS) have raised questions regarding the prevalence of pathogenic germline TP53 variants. We previously reported higher-than-expected population prevalence estimates in sequencing databases composed of individuals unselected for cancer history. This study aimed to expand and further evaluate the prevalence of pathogenic and likely pathogenic germline TP53 variants in the gnomAD dataset (n = 138,632). Variants were selected and classified based on our previously published algorithm and compared with alternative estimates based on three different classification databases: ClinVar, HGMD, and the UMD_TP53 website. Conservative prevalence estimates of pathogenic and likely pathogenic TP53 variants were within the range of one carrier in 3,555–5,476 individuals. Less stringent classification increased the approximate prevalence to one carrier in every 400–865 individuals, mainly due to the inclusion of the controvertible p.N235S, p.V31I, and p.R290H variants. This study shows a higher-than-expected population prevalence of pathogenic and likely pathogenic germline TP53 variants even with the most conservative estimates. However, these estimates may not necessarily reflect the prevalence of the classical LFS phenotype which is based upon cancer family history. Comprehensive approaches are needed to better understand the interplay of germline TP53 variant classification, prevalence estimates, cancer penetrance, and LFS-associated phenotype.
These findings suggest that anthropometric factors may have different associations with breast cancer risk in Hispanic women than in Caucasian women. This study also shows the importance of considering the evolution of body shape throughout life.
Breast cancer is a major public health problem in Latin America (LA) and the most common form of cancer among women. An important variability according to ethnicity/race with respect to incidence/mortality, clinical characteristics, and prognosis is observed throughout LA. In addition, women are more likely to develop breast cancer (BC) at younger age and to be diagnosed at an advanced stage compared to western women. While little is known about specific risk factors, changes in reproductive pattern (parity, breastfeeding) and lifestyle factors including sedentary behaviours, unhealthy diet, and alcohol intake may contribute to the increase of BC incidence. In this paper we give an overview of the burden and patterns of BC, review the leading causes of BC and discuss the possible ways to improve BC preven- tion and control in LA.
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