Humaid O Al-Shamsi1, Jeremy Jones2, Yazan Fahmawi3, Ibrahim Dahbour3, Aziz Tabash3, Reham Abdel-Wahab4, Ahmed O S Abousamra3, Kenna R Shaw5, Lianchun Xiao3, Manal M Hassan3, Benjamin R Kipp6, Scott Kopetz3, Amr S Soliman7, Robert R McWilliams2, Robert A Wolff3. 1. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA;; Khalifa Bin Zayed Al Nahyan Foundation, Abu Dhabi, United Arab Emirates;; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 2. Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA. 3. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA;; Clinical Oncology Department, Assiut University, Assiut, Egypt. 5. Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. 7. Department of Epidemiology, the University of Nebraska Medical Center, Omaha, Nebraska, USA.
Abstract
BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher's exact test was used to determine the association between mutation status and clinical features. RESULTS: A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. CONCLUSIONS: This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.
BACKGROUND: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. METHODS: Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher's exact test was used to determine the association between mutation status and clinical features. RESULTS: A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. CONCLUSIONS: This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.
Entities:
Keywords:
Arab population; Somatic mutations; colorectal cancer (CRC); next-generation sequencing (NGS)
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