Socioeconomic and Nutritional Factors Account for the Association of Gastric Cancer with Amerindian Ancestry in a Latin American Admixed Population

Latife Pereira,Douglas E Berg,Phabiola Herrera,Robert H Gilman,Fernanda Kehdy,Stephen J Chanock,Gloria Vargas,Juan M Combe,Silvana Schneider,Giordano Soares-Souza,William A Prado,Catherine C Hooper,Maira R Rodrigues,Lilia Cabrera,Roxana Zamudio,Jaime Cok,Eduardo Tarazona-Santos,Zongli Xu

doi:10.1371/journal.pone.0041200

Abstract

Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.

Highlights

Gastric cancer is one of the most lethal types of cancer, accounting for approximately 800,000 deaths per year, but its incidence varies substantially worldwide [1]
We determined that higher Native American individual ancestry is associated with gastric cancer, but that socioeconomic factors associated both with gastric cancer and ethnicity account for this association
We used a validated set of 103 ancestryinformative markers (AIMs) [26] to estimate Native American, European and Native American individual ancestry for each of the 241 gastric cancer cases and 300 controls recruited for this study

Summary

Introduction

Gastric cancer is one of the most lethal types of cancer, accounting for approximately 800,000 deaths per year, but its incidence varies substantially worldwide [1]. Helicobacter pylori diversity affects the risk of host gastric cancer, and the presence of the bacterial virulence factor cag+ is one of the most relevant risk factors While this virulence factor has a frequency of ,60% in European and US populations, it attains more than 90% in the Peruvian population [6]. While Native American individuals from isolated populations are infected by mostly native strains that resemble Asian strains, due to the Pleistocene Asian origin of Native Americans, individuals living in medium and large urban centers, even if they may have a predominant Native American ancestry, are infected by largely European or hybrid strains brought to the Americas after the 15th century These strains had largely replaced less virulent or vigorous native strains [7,8]

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Results

Conclusion