Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a mixed population of the Brazilian Amazon
Silva et al. BMC Res Notes
Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a mixed population of the Brazilian Amazon
Ellen Moreno da Silva 0 1 3 4 5
Marianne Fernandes Rodrigues 0 3 4
Darlen Cardoso de Carvalho 3 4
Luciana Pereira Colares Leitao 4
Giovanna Chaves Cavalcante 3
Esdras Edgar Batista Pereira 4
Antônio André Conde Modesto 3 4
João Farias Guerreiro 3
Paulo Pimentel de Assumpção 2 3 4
Sidney Emanuel Batista dos Santos 3 4
Ney Pereira Carneiro dos Santos 3 4
0 Ellen Moreno da Silva and Marianne Fernandes Rodrigues contributed
1 Instituto de Ciências Biológicas, Laboratório de Genética Humana e Médica , Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01, BOX: 8615, Belém, PA CEP 66.075‐970 , Brazil
2 Hospital Universitário João de Barros Barreto, Universidade Federal do Pará , Belém, PA , Brazil
3 Laboratório de Genética Humana e Médica, Universidade Federal do Pará , Belém, PA , Brazil
4 Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará , Belém , Brazil
5 Instituto de Ciências Biológicas, Laboratório de Genética Humana e Médica , Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01, BOX: 8615, Belém, PA CEP 66.075‐970 , Brazil
Background: Global literature describes differences in the incidence of gastric cancer among populations. For instance, Europeans have lower incidence rates of gastric cancer in relation to Latin and Asian populations, particularly Korean and Japanese populations. However, only a few studies have been able to verify the occurrence of gastric cancer in admixed populations with high interethnic degree mix, such as the Brazilian Amazon region. Results: We observed an increase in European ancestry in the control group compared to the case group (47% vs. 41%). Using increments of 10%, compared to categorical distribution of European ancestry in the sample, we found a difference in the contribution between cases and controls (p = 0.03). Multiple logistic regression was performed to determine the influence of European ancestry in susceptibility to gastric cancer in the sample. According to the adopted model, for each 10% increase in European ancestry, there is a 20% decrease chance of developing gastric cancer (P = 0.0121; OR = 0.81; 95% CI 0.54-0.83). Conclusion: Overall, the results suggest that a greater contribution of European ancestry can be a protective factor for the development of gastric cancer in the studied Amazon population. It can help to establish protocols able to predict susceptibility to gastric cancer in admixed populations.
Stomach cancer, also known as gastric cancer, is the third
leading cause of cancer death worldwide [
incidence of stomach cancer is the sixth highest in the world
] and is among the highest incidences in Latin America
The literature reports differences in the incidence of
gastric cancer among populations. For example,
Europeans have lower rates of gastric cancer incidence when
compared to Latin and Asian populations, especially
Japanese and Korean [
]. These differences in incidence
can be attributed to risk factors associated with lifestyle,
such as diet, obesity, stress and physical inactivity. In
addition, other studies suggest that the lower incidence of
gastric cancer in the European population may be related
to lower frequency of genes associated with gastric
cancer susceptibility [
In this context, it is conceivable that heterogeneity
among populations and different genetic ancestries can
contribute to the varying levels of susceptibility to
cancer development. This is especially important in admixed
populations, such as the Brazilian population, which is
known to be one of the most heterogeneous populations
in the world, with contributions from three main
parental groups: Amerindian, European and African [
Literature demonstrates the influence of genetic ancestry
and the risk of developing various types of cancer, such as
], colorectal [
], leukemia [
ovarian cancer [
]. More specifically, there is a work that
explores the influence of genetic ancestry in the risk of
developing gastric cancer among Brazilian populations
Therefore, the objective of this study is to investigate
the influence of genetic ancestry in susceptibility to
gastric cancer in a population of the Amazon region with a
high degree of interethnic admixture.
Cases and control
The participants of the research were chosen based on
a case–control study. Participants from both case and
control groups were recruited from free services in
public institutions, were from the same socioeconomic level,
and belonged to the same geographic area.
The case group constituted of 137 individuals that were
diagnosed with gastric adenocarcinoma, attended by the
Unified Health System (SUS), in a public hospital that is
reference in the treatment of this kind of neoplasm
(Hospital Universitário João de Barros Barreto, Pará, Brazil).
Most patients involved in the study (80%) presented
advanced tumor staging—grade III and IV according to
The control group constituted of 262 cancer-free
individuals, attended in the Laboratório de Exercício
Resistido e de Saúde (LERES), from a public university of the
region (Universidade Estadual do Pará, Pará, Brazil).
The protocol used in the study was approved by the
Ethics Committee of the University Hospital João de Barros
Barreto (Protocol Number 3505/2004). All patients in the
present study signed a consent form.
Analysis of genetic ancestry
The analysis of genetic ancestry was performed using a
panel of 48 ancestry informative markers (AIM)
developed by Santos et al. [
]. Amplification was performed
using three multiplex PCR reactions with 16
markers each. PCR separation and analysis was performed
by capillary electrophoresis using the ABI PRISM 3130
sequencing and GeneMapper ID Software v3.2.
Individual proportions of ancestries of Europeans, Africans
and Amerindians were estimated using the STRUCTURE
software v2.3.3, with three parental populations
(European, African and Amerindian).
Parental populations involved individuals that were
representative of three great ancestral groups: 222
Amerindian from nine tribes in the Brazilian Amazon (Tiriyó,
Waiãpi, Zoé, Urubu-Kaapor, Awa-Guajá, Parakanã, Wai
Wai, Gavião and Zoró), 211 African (Angola,
Mozambique, Congo Republic, Cameroon and Ivory Coast) and
268 European (Portugal and Spain). More details on these
populations can be found in [
All statistical analyses were performed using the
statistical program SPSS v.20.0 (SPSS, Chicago, IL. USA). Chi
squared test in pairs was applied for group comparisons
of categorical variables (sex), while Student’s t-test was
used for the analysis of quantitative variables (age). For
comparisons of ancestry among the samples, we used the
Mann–Whitney test. Multiple logistic regression
analyses were performed to estimate odds ratios (ORs) and
95% confidence intervals (CIs). In these analyses,
variables considered confounding factors (age, sex) were
corrected. All statistical tests were two-tailed and based on
P < 0.05 probability to be significant.
We analyzed 137 patients with gastric cancer and 262
cancer-free individuals. Table 1 shows the demographic
characteristics of these groups. The case group showed
a predominance of men while the control group showed
a predominance of women. The results were statistically
significant between the case and control groups
regarding the following variables: age (P < 0.001), sex (P < 0.001)
and European ancestry (P = 0.001).
According to the ancestry analyses conducted in this
study, the ethnic composition of the case group was 41%
European, 26% African and 33% Amerindian. By
comparison, the control group’s ancestry contributions was 47%
European, 23% African and 30% Amerindian (Table 1).
The results revealed that there was a higher
contribution of European ancestry in the control group
compared to the case group (47% vs. 41%). Using increments
of 10%, we compared the categorical distribution of
a Values are as expressed as mean (± SD = standard deviation). Significance
determined by Student’s t-test
b Values are as expressed as mean ± SD. Significance determined by Mann–
European ancestry in the sample and found a difference
in this ancestry contribution between cases and controls
(P = 0.03) (Table 2).
Multiple logistic regressions were performed to
determine the influence of European ancestry in the
susceptibility to gastric cancer in the sample (Table 3). According
to the adopted model, for each 10% increase in European
ancestry there is a 20% lower chance of developing
gastric cancer (P = 0.0121; OR = 0.81; 95% CI 0.68–0.95).
In our analyses, the case group presented a greater
proportion of men (75%), while in the control group, the
proportion was greater among women (60%). The
incidence of gastric cancer, as well as other gastrointestinal
neoplasms, was greater in men than in women. This
finding has been observed in different populations worldwide
]. The justification for this disparity in incidence
between men and women goes beyond the explanation of
sex differences for exposure to known risk factors. Many
studies have suggested a protective effect of estrogen in
the development of gastric cancer [
To better comprehend the sex difference in the
susceptibility to gastric cancer, we performed new statistical
tests, which included isolated analyses for men
(Additional file 1) and for women (Additional file 2). In both
men and women, the European ancestry was the most
prevalent, being more frequent in the control group than
in the case group.
In the analyses involving only men (Additional file 1),
European ancestry was statistically different between
case and control (P = 0.009). Logistic regression
analysis showed a reduction of 94% in the chances of
developing gastric cancer (P = 0.004; OR = 0.059; 95% CI
In the analyses involving only women (Additional
file 2), there was no statistically significant difference
of European ancestry between case and control groups
(P = 0.052). We believe that the absence of significance
may be due to the low sample number of women in the
case group (N = 34), which may not allow reliable
Brazilian population is one of the most heterogeneous
populations worldwide and it is formed by an admixture
of Amerindians, Europeans and Africans. The admixture
process occurred through different means in the
Brazilian geographic regions. Our sample presented a variety
in its composition, with a higher prevalence of European
ancestry, followed by Amerindian and African
ancestries in both case and control groups (Fig. 1). Previous
data have demonstrated that the European ancestry is
predominant in four regions in Brazil—North (68.8%),
Northeast (60.1%), Southeast (74.2%) and South (79.5%).
The African proportion was highest in the Northeast
(30.3%) and the Amerindian proportion was highest in
the North (19.4%) [
Our results demonstrated that European ancestry is
more represented in the control group than it is in the
case group (Table 1) and that genetic ancestry modifies
the risk of developing gastric cancer. The 10% increase in
European ancestry was associated with decreased risk of
developing gastric cancer (Table 3). There are only a few
works in literature on the association of genetic ancestry
and gastric cancer susceptibility [
The work by [
] has investigated the susceptibility to
gastric and breast cancer together, in a different population
from the North region of Brazil, and found a protection
association between European ancestry and the development
of these neoplasms. Each increase of 10% in the European
ancestry was inversely correlated to the risk of developing
cancer (OR = 0.186), corroborating with our results.
A work developed by [
] has investigated the
contribution of genetic ancestry in the risk of developing
gastric cancer in an admixed population from Lima (Peru).
European ancestry was correlated to a negative effect in
the development of gastric cancer, supporting our results.
In addition, other studies have analyzed the association
of genetic ancestry and cancers around the world. For
example, African ancestry was associated with colorectal
] and with prostate cancer [
ancestry was associated with the development of acute
lymphoblastic leukemia (ALL) [
Our results showed that genetic ancestry may modify
the risk of developing gastric cancer. European ancestry
was related to a reduction in the chances of developing
this neoplasm. Further studies must be carried out to
identify genetic polymorphisms that are more frequent
in populations with high European ancestry and that may
confer a protective effect to this ancestry regarding the
development of gastric cancer.
Our results corroborate with studies that suggest that the
lower incidence of gastric cancer in the European
population may be related to lower frequency of alleles related to
high susceptibility of developing gastric cancer [
Therefore, a higher European ancestry contribution may be
considered a protection factor to gastric cancer in the studied
Amazon population. More studies are needed to confirm
such results, but this work presented significant findings
that contribute to a greater knowledge of the influence of
genetic ancestry in the development of gastric cancer.
Additional file 1. Demographic variables for men in both groups (gastric
cancer and control). To better comprehend the sex difference in the
susceptibility to gastric cancer, we performed new statistical tests, which
included isolated analyses for men.
Additional file 2. Demographic variables for women in both groups
(gastric cancer and control). To better comprehend the sex difference in
the susceptibility to gastric cancer, we performed new statistical tests,
which included isolated analyses for women.
ALL: acute lymphoblastic leukemia; PCR: polymerase chain reaction; OR:
All the authors listed, contributed significantly with the preparation of the arti‑
cle: EMS and MFR conducted the survey, data analysis, and wrote the manu‑
script; DCC, GCC, LCL, EEBP, AACM, JFG and PPA analyzed the data, performed
statistical analysis and edited the manuscript; SEBS and NPCS reviewed the
statistical analysis, edited and approved the manuscript. All authors read and
approved the final manuscript.
We are grateful to the communities studied for their collaboration.
The authors declare that they have no competing interests.
Availability of data and materials
All data generated or analyzed during this study are included in this published
article and its additional files.
Consent for publication
Ethics approval and consent to participate
The protocol used in the study was approved by the Ethics Committee of
the University Hospital João de Barros Barreto (Protocol Number 3505/2004).
All patients in the present study signed a consent form for the collection of
biological samples and clinical records of medical records.
Fundação Amazônica Paraense do Estado do Pará (FAPESPA); Coordenação
de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Pró Reitoria de
Pesquisa (PROPESP) and Pós‑ Graduação em Genética e Biologia Molecular
(PPGBM) of Universidade Federal do Pará.
Springer Nature remains neutral with regard to jurisdictional claims in pub‑
lished maps and institutional affiliations.
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