K-RAS Mutation Profile in Puerto Rican Patients with Colorectal Cancer: Trends from April 2009 to January 2011

Abstract

The frequency of K-RAS mutations ranges between 30% and 48% among the Caucasian, Asian, and European populations and these mutations are predictors of response to EGFR therapies. We sought to determine the expression of K-RAS gene mutations among colorectal cancer patients in PuertoRico. A retrospective study was conducted to determine the expression of mutant K-RAS among colorectal cancer patients in Puerto Rico between April 2009 and January 2011. The mutant expression of K-RAS was found in 39% (n=195) of the Puerto Rican population, and was more common in the age group of 51–69 years (53.8%) and in males (55.4%, p>0.05). Moreover, mutant K-RAS was more commonly found in tumors of the proximal area (43.8%; p=0.03), with distant metastasis (43.3%, p=0.018), with a mucinous histotype (31.7% p>0.05), and in ulcerated tumors (38.8%, p>0.05). K-RAS mutations were observed on codon 12 (87.7%) and codon 13 (12.3%). The most frequent mutation on codon 12 was 12 ASP (39.5%), followed by 12 VAL (25.4%) that is associated with a significant decrease in overall cancer survival. The mutant expression of K-RAS in cases of rectum carcinoma was 39.5%, where the most common mutation was 12 VAL (37.5%). The frequency of K-RAS mutations in the Puerto Rican population here studied was 39% and mutant K-RAS was associated with advanced colorectal cancer stage, mucinous histotype, and ulcerated tumors.

Frequency and Clinical Impact of KRAS Mutations in Patients with Colorectal Cancer from the Middle East

“…In a much smaller sample of 46 patients, we found that males are more likely to have mutant KRAS status than females [37]. Association between mutations and male gender was also reported in the Puerto Rican patient population [38].…”

“…For example KRAS mutations correlated with regional lymph node metastasis and tumor stages in 88 patients from Sweden and 99 patients from Japan [49]. In a study of 501 Puerto Rican patients, mutation were detected more frequently in patients with distant metastases compared to those without (50% vs. 37.4%; P=0.020) [38]. Another series of 254 Japanese patients also reported a significant association between poor RFS and MT KRAS [50].…”

Molecular profiling of colorectal cancer in a genetically admixed Hispanic population

“…We also compared the mutational frequencies of actionable genes for CRC and reported significant differences for PRH in KRAS/NRAS , BRAF , and ERBB2 amplification. The high mutational frequency of KRAS reported for PRH differs from a previous study with PRH that found KRAS mutations in 39% of CRC tumors 40 . However, a similar KRAS mutational frequency was reported for USH (59%), 41 while a higher frequency was reported for Mexicans (86%) 42 .…”

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

“…Overall, KRAS mutation frequencies in our PRH cohort (31.9%) are lower than those reported in other racial/ethnic groups, including non-Hispanic Blacks (59%) and non-Hispanic Whites (37–41%) [ 33 , 34 , 35 , 41 ]. A previous study in a separate cohort of 501 PRH reported a slightly higher but comparable prevalence of KRAS mutations (39%) [ 42 ]. The percentage of tumors with MSI in our cohort was markedly lower (4.3%) than what has been reported in African Americans (14–19%) and non-Hispanic Whites (9–13%) [ 33 , 37 , 43 , 44 ].…”