Association between tumor mutation profile and clinical outcomes among Hispanic-Latino patients with metastatic colorectal cancer (2025)

Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico

Genes, 2023

Mutation profiling of cancer drivers in Brazilian colorectal cancer

Scientific Reports, 2019

The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite instability (MSI) and genetic ancestry in a series of 91 Brazilian CRC patients. Driver mutations were found in the APC (71.4%), TP53 (56.0%), KRAS (52.7%), PIK3CA (15.4%) and FBXW7 (10.9%) genes. Overall, genes in the MAPK/ERK, PIK3/AKT, NOTCH and receptor tyrosine kinase signaling pathways were mutated in 68.0%, 23.1%, 16.5%, and 15.3% of patients, respectively. MSI was found in 13.3% of tumors, most of which were proximal (52.4%, P< 0.001) and had a high mutation burden. European genetic ancestry was predominant (median of 83.1%), followed by Native American (4.1%), Asian (3.4%) and African (3.2%). NF1 and BRAF mutations were associated with African ancestry, while TP53 and PIK3CA mutations were inversely correlated with Native American ancestry. Our study suggests that Brazilian CRC patients exhibit a mutation profile similar to other populations and identify the most frequently mutated genes, which could be useful in future target therapies and molecular cancer screening strategies. Colorectal cancer (CRC) is the third most common type of cancer worldwide 1,2. According to GLOBOCAN, over 1.8 million new colorectal cancer cases occurred in 2018. Moreover, the disease is the second cause of death by cancer worldwide 2. Increases in both incidence and mortality have been observed over the last 10 years in several Europe, Latin America, and Asia countries 1. The most significant increases in incidence were observed in Brazil, Costa Rica and Bulgaria 1. In Brazil, the Brazilian National Cancer Institute (INCA) estimated that over 36,000 new cases were expected for 2018, ranking CRC as the third most frequent cancer among men and as the second most frequent cancer among women 3. CRC is more frequently observed in the distal colon (left colon, from splenic flexure to rectum) than in the proximal side (right colon, from the cecum to transverse colon) 4. In addition to incidence differences, the tumors arising from the left and right colon are distinct in their epidemiology, biology, histology and microbial diversity 4-7. Consequently, it also influences patients' prognosis 4,8. Several lifestyles are risk factors associated with CRC, such as red and processed meat consumption, alcohol intake, smoking and body weight 9. Moreover, the cumulative acquisition of genetic alterations leads to a progressive tumorigenesis process from normal to precursor lesion, culminating in a malignant tumor 10. The majority (80-85%) of CRC cases are sporadic and emerge from somatic alterations in driver genes 10. These alterations are linked to three main molecular groups: chromosomal instability, mismatch repair defect and methylator phenotype 7,10. In addition to these classic features, the CRC Subtyping Consortium classified four consensus molecular subtypes (CMS) of CRC: CMS1, which are enriched for tumors with MSI, overexpression of DNA damage repair proteins, high immune activation and widespread hypermethylation; CMS2, which have tumors with chromo-somal instability and activation of the WNT and MYC signaling pathways; CMS3, with tumors with epithelial and metabolic dysregulation; and CMS4, which have tumors with transforming growth factor-β activation, stromal infiltration and angiogenesis 6. The molecular profile of CRCs is distinct between proximal and distal tumors. Proximal CRCs are associated with microsatellite instability (MSI) and activating mutations on the BRAF gene, frequently harboring a high mutation burden, whereas distal CRCs are associated with chromosomal instability

Racial Differences in BRAF/KRAS Mutation Rates and Survival in Stage III Colon Cancer Patients

Journal of the National Cancer Institute, 2015

It is unknown if, after controlling for clinicopathologic variables and treatment, racial disparities in colon cancer outcomes persist. Molecular marker analysis in North American patients comparing Asians with other races has not been reported. BRAF (V600E) and KRAS mutations were analyzed in node-positive colon cancer patients (n = 3305) treated with FOLFOX-based chemotherapy in an adjuvant trial (Alliance N0147). Race categories included Asian, black, or white. Cox models were used to estimate disease-free survival (DFS) and time to recurrence (TTR). All statistical tests were two-sided. BRAF mutation frequency in tumors from whites (13.9%) was twice that of tumors from Asians or blacks. KRAS mutation rates were highest in tumors from blacks (44.1%). KRAS/BRAF wild-type tumors were most common among Asians (66.7%) (P overall &lt; .001). The prognostic impact of race differed by age and N stage (both P interaction &lt; .02). Compared with whites, blacks had shorter DFS among patie...

Disparities in incidence of early- and late-onset colorectal cancer between Hispanics and Whites: A 10-year SEER database study

The American Journal of Surgery, 2017

Abstract C30: Disparities in colorectal cancer survival among Puerto Rican Hispanics

Cancer Epidemiology, Biomarkers &amp; Prevention, 2016

Background: Ethnic/racial disparities in colorectal cancer (CRC) survival have been well documented. In Puerto Rico (PR), CRC is the leading cause of cancer death in men and women. This study reports the 5-year relative survival of Puerto Rican Hispanic (PRH) CRC patients compared to other US racial/ethnic groups and estimates the mortality hazard ratio by sex, age, and tumor stage at diagnosis. Methods: CRC incidence data from subjects &gt;50 years was obtained from the Puerto Rico Central Cancer Registry from January 1, 2001 to December 31, 2003. CRC incidence and mortality data for US Hispanics (USH), non-Hispanic White (NHW) and non-Hispanic black (NHB) during the same period were obtained from the Surveillance, Epidemiology and End Results (SEER) database. One-, three- and five-year relative survival rates were calculated using the life tables from the population of PR and SEER. In addition, a Cox proportional hazards model was employed to assess mortality hazard ratio by sex, ...

Disparities in colon and rectal cancer queried individually between Hispanics and Whites

Journal of Gastrointestinal Oncology, 2019

Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians

npj Precision Oncology

In the US, the majority of cancer samples analyzed are from white people, leading to biases in racial and ethnic treatment outcomes. Colorectal cancer (CRC) incidence and mortality rates are high in Alabama African Americans (AAs) and Oklahoma American Indians (AIs). We hypothesized that differences between racial groups may partially explain these disparities. Thus, we compared transcriptomic profiles of CRCs of Alabama AAs, Oklahoma AIs, and white people from both states. Compared to CRCs of white people, CRCs of AAs showed (a) higher expression of cytokines and vesicle trafficking toward modulated antitumor-immune activity, and (b) lower expression of the ID1/BMP/SMAD axis, IL22RA1, APOBEC3, and Mucins; and AIs had (c) higher expression of PTGS2/COX2 (an NSAID target/pro-oncogenic inflammation) and splicing regulators, and (d) lower tumor suppressor activities (e.g., TOB2, PCGF2, BAP1). Therefore, targeting strategies designed for white CRC patients may be less effective for AAs/...

Association of genetic ancestry with colorectal tumor location in Puerto Rican Latinos

Human Genomics, 2019

Mismatch repair protein expression and colorectal cancer in Hispanics from Puerto Rico

Familial Cancer, 2010

Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.

Mutational analysis and clinical correlation of metastatic colorectal cancer

Cancer, 2014

BACKGROUNDEarly identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes.METHODSUnder Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for &gt;150 mutations across 15 commonly mutated cancer genes. The chi‐square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival.RESULTSBroad‐based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with re...