Accurateness and thoroughness marked the stages of the research project carried out for five years by Universidad Nacional de Colombia (UNal) Sciences-Chemistry Ph.D. María Carolina Sanabria Salas. It was key to take care of up to the last detail with the purpose of coordinating the gathering and comparison of 1,000 blood samples both for healthy individuals as with colorectal cancer patients –the fourth most common cancer in men and third in women in Colombia– from Bogotá, Bucaramanga, Cali, Santa Marta, Barranquilla and Cartagena.
The research team characterized the ancestry distribution of profiles taking into account the high miscegenation across history. For instance, in the Andean region, 60% is from European descent, 37% Amerindian and 3% African; in the Caribbean region, 48% are European, 31% Amerindian and 21% African and in the city of Cali, 40% European, 38% Amerindian and 22% African.
The project had an ambitious goal: Establish how the genetic ancestry impacted Colombians on the incidence of the disease, whose mortality rate increased significantly among men (2.2%) and women (1.9 %) in the 1985-2006 time period.
After performing a statistical analysis among 1,000 people, of which 500 were healthy, 300 had colorectal cancer and 200 with adenomatous polyps (intestinal masses that need to be removed to avoid progression to cancer), they observed that a larger African ancestry is related to the greater threat of colorectal cancer and adenomatous polyps.
“The African ancestry percentage in an individual is the part of its genetic material which he/she inherited from its African forefathers,” said the researcher.
Sanabria carried out an association measurement whose values over 1.0 are suggestive of a greater threat. With African ancestry, this value is between 1.03 and 1.17 for colorectal cancer and between 1.03 and 1.21 for adenomatous polyps.
This first approach ratifies results from other research projects; for instance in 2008, the American Society of Clinical Oncology indicated that the prevalence of this type of cancer in African Americans was greater than 50% with respect to white people.
To establish a convincing “why” for the Colombian case requires more research said Dr. Sanabria, “Before coming to America, Africans evolved and lived a different scenario, which was configured in their genetic profile. The same thing happened with Europeans and Indians.”
Naturally the genetic factor is not the only determining element; unhealthy life habits such as a diet rich in fat and low in fiber as well as drinking and smoking, besides reduced access to the healthcare system may propitiate this silent disease, while the patient begins to have silent alarm signals such as thin feces with blood, sensation of intestinal fullness, abdominal pain, abdomen masses, loss of weight, tiredness, nausea, vomit, and anemia.
Following the study line, they can determine the most vulnerable communities and establish specific preventive measures. For instance, during the 2007-2011 period, the Province of Valle del Cauca had one of the highest incidences of colorectal cancer in the country: 14.9% in men and 15.3 in women, and a mortality rate of 7.3% in men and 7.5% in women. It is also necessary to say that Cali, its capital, has the greatest percentage of Afro-descendants with close to 26% of the population.
Using a software program they established two genetic markers associated with a greater susceptibility to colorectal cancer and adenomatous polyps. They are a genetic variant located in gene TEP1, on chromosome 14, and the other on gene TK1, located on chromosome 17. In both cases, the most frequent allele is linked to greater risk of colorectal tumors.
The two genetic variables proposed are combined with a world database of 63 common genetic variants –different to high-risk mutations for the development of the disease– related to the risk of colorectal cancer. This information could be used to design a multi-locus platform (including the simultaneous research of variants) with the purpose of determining which are the most vulnerable individuals, in other words, the ones with the greatest number of said variations.
Taking advantage of the authorization provided by the participants of the study for use of their samples, the scientific team went beyond and determined three protein biomarkers in blood plasma with the purpose of offering new alternatives for the follow-up of the disease. This second phase was applied to 20 individuals with cancer and 6 healthy individuals.
The discovered that fibulin-1 was lower in affected individuals, which is linked to greater invasion capability of cancerous cells and therefore a worse diagnostic. They also discovered higher levels of CD14 and LV401 proteins in colorectal cancer patients. The former favors the inflammation processes and the second could be a reflection of the capability of malignant cells to produce factors which promote its growth. The preceding corresponds to reports found in scientific literature.
Dr. Sanabria and Professor Adriana Umaña Pérez, researcher of the UNal Hormone Research Group, are pleased of the possibility that this study, from the National Cancer Institute, was carried out, for the first time in Colombia, but they clarify that this is just the beginning of an investigation line which needs to approach new perspectives with a greater sample.
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