An Atypical Age-Specific Pattern of Hepatocellular Carcinoma in Peru: A Threat for Andean Populations

Abstract

BackgroundIn South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country.MethodsA retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin.ResultsSurprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics.ConclusionsThe analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.

Recent advances in the molecular mechanism of sex disparity in hepatocellular carcinoma (Review)

“…In contrast to the tumor-promoting activity of the androgens, the preventive and inhibitory effects of estrogen have been epidemiologically demonstrated by studies revealing an increased incidence of HCC following the menopause (12)(13)(14). This is consistent with animal studies in which treatment with estrogen decreased the incidence and metastasis of HCC, and ovariectomy increased susceptibility to HCC in female mice (15).…”

A Peculiar Mutation Spectrum Emerging from Young Peruvian Patients with Hepatocellular Carcinoma

“…Straight line represents the histogram curve fitting with a Gaussian mixture function (BI = 1.8). This bimodal distribution concurs with the observation previously made in Peru [6] . ( B,C ) Distribution maps of the population size (B) and mean age (C) of the patients according to their regional origin.…”

“…Exceeding serum AFP concentration is another hallmark of the tumorigenic process ongoing in Peruvian patients and can provide some substantial insights regarding the molecular bases of the disease [6] . Given the young age of many patients, we first assessed whether AFP mRNA could be expressed in NTL of <40 patients with high value of circulating AFP.…”

“…Surgeons of the National Cancer Institute of Peru (INEN), the major Peruvian cancer center, have recently described a locally frequent, but elsewhere unusual, form of HCC affecting children, adolescents, and young adults [5] . We then reported that age-specific distribution of HCC in Peruvian patient population was delineating a bimodal distribution, with a first peak of incidence at age 25 and a second one at age 64 [6] . These HCC cases appearing in younger patient population were characterized by a tremendous elevation of alpha-fetoprotein (AFP) tumor marker serum concentration, the absence of cirrhosis in 95% of the cases, and the presence of an associated risk factor [mostly HBV surface antigen (HBsAg) carriage] in merely 50% of cases [6] .…”

Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation

“…The present study investigating the effects of simultaneous folate deficiency or supplementation and aging on DNA methylation and in turn its effects on liver folate transport system under chronic conditions, is of importance in understanding the epigenetic basis of liver pathologies with aging. Moreover, alterations in DNA methylation due to malnutrition and aging are linked to neurological defects and human cancers including that of liver cancer . In conclusion, our study demonstrates that folate deficiency alters the expression of folate transporters RFC and folate exporter ABCG2 in the AG differently than WG and YG both at the transcriptional and translational level, which in turn was found to be epigenetically regulated by promoter methylation of the RFC and ABCG2 genes.…”