Distribution of allelic and genotypic frequencies of IL1A, IL4, NFKB1 and PAR1 variants in Native American, African, European and Brazilian populations

Abstract

Background The inflammatory response plays a key role at different stages of cancer development. Allelic variants of the interleukin 1A (IL1A), interleukin 4 (IL4), nuclear factor kappa B1 (NFKB1) and protease-activated receptor 1 (PAR1) genes may influence not only the inflammatory response but also susceptibility to cancer development. Among major ethnic or continental groups, these polymorphic variants present different allelic frequencies. In admixed populations, such as the Brazilian population, data on distribution of these polymorphisms are limited. Here, we collected samples of cancer-free individuals from the north, northeast, midwest, south and southeast regions of Brazil and from the three main groups that gave rise to the Brazilian population: Native Americans from the Brazilian Amazon, Africans and Europeans. We describe the allelic distributions of four IL1A (rs3783553), IL4 (rs79071878), NFKB1 (rs28362491) and PAR1 (rs11267092) gene polymorphisms, which the literature describes as polymorphisms with a risk of cancer or worse prognosis for cancer.ResultsThe genotypic distribution of the four polymorphisms was statistically distinct between Native Americans, Africans and Europeans. For the allelic frequency of these polymorphisms, the Native American population was the most distinct among the three parental populations, and it included the greatest number of alleles with a risk of cancer or worse prognosis for cancer. The PAR1 gene polymorphism allelic distribution was similar among all Brazilian regions. For the other three markers, the northern region population was statistically distinct from other Brazilian region populations.ConclusionThe IL1A, IL4, NFKB1 and PAR1 gene polymorphism allelic distributions are homogeneous among the regional Brazilian populations, except for the northern region, which significantly differs from the other four Brazilian regions. Among the parental populations, the Native American population exhibited a higher incidence of alleles with risk of cancer or worse prognosis for cancer, which can indicate greater susceptibility to this disease. These genetic data may be useful for future studies on the association between these polymorphisms and cancer in the investigated populations.

Effect of genetic ancestry to the risk of susceptibility to gastric cancer in a mixed population of the Brazilian Amazon

“…Parental populations involved individuals that were representative of three great ancestral groups: 222 Amerindian from nine tribes in the Brazilian Amazon (Tiriyó, Waiãpi, Zoé, Urubu-Kaapor, Awa-Guajá, Parakanã, Wai Wai, Gavião and Zoró), 211 African (Angola, Mozambique, Congo Republic, Cameroon and Ivory Coast) and 268 European (Portugal and Spain). More details on these populations can be found in [ 17 ].…”

Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer

“…PAR-1 signaling induced expression of integrin IIb3 and P-selectin promoted melanoma cell-EC/platelet interaction, thereby increasing the metastatic potential of cancer cells [ 33 – 34 , 45 , 52 – 53 ]. Overexpression of NF-κB, EGFR can activate PAR-1 signaling, which consequently promotes tumor cell growth and invasion [ 54 ]. In contrast to normal tissue, STAT3-dependent transactivation of EGFR and PAR-1 in endothelial cells of clear cell renal cell carcinoma was significantly increased [ 55 ].…”

Genetic polymorphism of calcium-sensing receptor in women with breast cancer

“…The distribution of genetic variants differs between populations of diverse ethnic and geographic backgrounds. Genetic variants in the Brazilian population do not commonly show a consistent pattern of distribution due to widespread miscegenation, since it differs from other countries where populations are predominantly Caucasian, African or Asian [14,15]. CaSR gene polymorphism has been related to increased calcium levels, reduced calcium-sensing receptor expression and a higher breast cancer risk and tumor aggressiveness [16].…”