Molecular Subtypes and Driver Mutations in Latinos with Gastric Cancer: Implications for Etiological and Translational Research
Gastric cancer (GC) is a leading cause of mortality and a malignancy that disproportionally affects Latino populations in the United States and Latin America. Latinos are two times more likely to be diagnosed with and to die of GC than non-Latino whites (NLW). Published data and ongoing research suggest that the molecular epidemiology of GC in Latinos is unique. Here we present an overview of GC epidemiology and disparities and describe our pilot data on Latino GC genomics. Also discussed are research gaps in etiology and translational research that need to be addressed to improve GC outcomes in Latino populations.
KeywordsGastric cancer Cancer disparities Latinos Molecular epidemiology Molecular classification
Gastric Cancer Is a Common Malignancy with Poor Outcomes
Worldwide, gastric cancer (GC) is the third leading cause of cancer mortality . Each year ~1 million new gastric cancer (GC) cases are diagnosed and >720,000 patients die of GC [2, 3]. GC prognosis is dismal because early-stage tumors, where survival is high, are clinically silent and difficult to detect. Most GCs are detected in late stages and have 5-year survival rates <10% [2, 4, 5]. To improve GC outcomes, major limitations need to be addressed. First, new prevention and early detection tools must be developed, including the identification of susceptibility genes that allow the identification of high-risk individuals. Until recently, E-cadherin (also known as CDH1) was the only known GC gene; it accounts for ~40% of cases with hereditary diffuse GC (HDGC) syndrome and a very small fraction of non-HDGC cases [2, 6, 7]. We recently identified a second familial GC form, involving germline mutations in recombination DNA repair genes, which account for ~2–6% of all cases [1, 8, 9]. Even though this recent gene discovery represents an important advance, few individuals currently benefit from genetic-guided prevention. Another major limitation is the need to develop effective therapies to improve GC outcomes. The Cancer Genome Atlas (TCGA) study found that >70% of all GCs have mutations that can be targeted with existing drugs . Despite this large fraction of “druggable” mutations, only two GC-targeted therapies have been approved by the Food and Drug Administration (FDA) [11, 12]. Hence, major advances in etiological and translational research are needed to improve GC outcomes through prevention, early detection, and better treatments.
Gastric Cancer in Latinos
Disparities in gastric cancer incidence and mortality in Latinos and in non-Latino whites (NLW ) (data from the American Cancer Society report )
Incidence per 100,000 individuals
Mortality per 100,000 individuals
Genomic and Genetic Research Disparities
The racial/ethnic composition of the GC patients included in TCGA 
Fraction of patients (n = 295) (%)
Non- Latino whites
The Unique Epidemiology of Gastric Cancer in Latinos
Epidemiological profiles of gastric cancers in Latinos and NLWs from California (2010–2014) (data from )
Latinos (n = 3879)
NLW (n = 4612)
Early onset (≤50 years)
Late onset (>50 years)
Molecular GC Profiles in Latinos Are Unique
Mutation frequency data of known gastric cancer driver genes in Latinos and TCGA (Luis Carvajal-Carmona laboratory, unpublished)
TCGA (n = 295)
Latinos (n = 30)
Latinos have the highest GC burden in the United States. Published data and ongoing research suggest that the epidemiology of GC in Latinos is unique. It is now critically important to carry out studies that help us understand the etiology of GC in this minority population and that further characterize genetic and genomic patterns in GC patients of Latino ancestry. Furthermore, the unique molecular patterns in Latino GCs warrants future preclinical and translation studies in driver genes and molecular subtypes that are more prevalent in this minority population.
I am indebted to all my collaborators and to the participants in our studies. I am grateful for research funding from the University of California, Davis (School of Medicine Dean’s Fellowship in Precision Health Equity; Office of the Provost supported Latino Cancer Health Equity Initiative); COLCIENCIAS (Project Evaluacion de exoma de pacientes Colombianos con cancer gastrico y de genoma de Helicobacter pylori, code 110565843382, contract 204-2015) and from the National Cancer Institute (grants R01CA223978, R21CA199631, U54CA233306, and P30CA093373) and from the National Institute of Environmental Health Sciences (grant P30ES023513) of the National Institutes of Health. The content of this chapter is solely the responsibility of the author and does necessarily represent the official views of the National Institutes of Health.
- 11.Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.CrossRefGoogle Scholar
- 12.Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–9.CrossRefGoogle Scholar
- 13.González Burchard E, Borrell LN, Choudhry S, Naqvi M, Tsai H-J, Rodriguez-Santana JR, Chapela R, Rogers SD, Mei R, Rodriguez-Cintron W, Arena JF, Kittles R, Perez-Stable EJ, Ziv E, Risch N. Latino Populations: A Unique Opportunity for the Study of Race, Genetics, and Social Environment in Epidemiological Research. American Journal of Public Health. 2005; 95(12):2161–8.CrossRefGoogle Scholar
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