Abstract
Admixed populations have not been examined in detail in cancer genetic studies. Here, we inferred the local ancestry of cancer-associated single nucleotide polymorphisms (SNPs) and haplotypes of a highly admixed Brazilian population. SNP array was used to genotype 73 unrelated individuals aged 80-102 years. Local ancestry inference was performed by merging genotyped regions with phase three data from the 1000 Genomes Project Consortium using RFmix. The average ancestry tract length was 9.12-81.71 megabases. Strong linkage disequilibrium was detected in 48 haplotypes containing 35 SNPs in 10 cancer driver genes. All together, 19 risk and eight protective alleles were identified in 23 out of 48 haplotypes. Homozygous individuals were mainly of European ancestry, whereas heterozygotes had at least one Native American and one African ancestry tract. Native-American ancestry for homozygous individuals with risk alleles for HNF1B, CDH1, and BRCA1 was inferred for the first time. Results indicated that analysis of SNP polymorphism in the present admixed population has a high potential to identify new ancestry-associated alleles and haplotypes that modify cancer susceptibility differentially in distinct human populations. Future case-control studies with populations with a complex history of admixture could help elucidate ancestry-associated biological differences in cancer incidence and therapeutic outcomes.
Highlights
Cancer is the second leading cause of death in developing countries, and its incidence is expected to increase by 75% by 2030 because of risk-associated lifestyle behaviors and the aging of the world’s population (Bray et al, 2012; Cai and Liu, 2019; Torre et al, 2015)
For the HNFB1 gene, 47 (64.38%) haplotypes were of European ancestry, 14 (19.17%) European / African, six (8.21%) European / admixed Native American, two haplotypes (2.73%) African and two (2.73%) African / admixed Native American, one haplotype (1.36%) European / Unknown and one (1.36%) African / Unknown
For the BRCA1 gene, 37 (50.68%) haplotypes were of European descent, 22 (30.13%) European / African, five (6.84%) European / admixed Native American, five haplotypes (6.84%) were Africans, two (2.73%) African / admixed Native American and one haplotype (1.36%) of admixed Native American ancestry
Summary
Cancer is the second leading cause of death in developing countries, and its incidence is expected to increase by 75% by 2030 because of risk-associated lifestyle behaviors and the aging of the world’s population (Bray et al, 2012; Cai and Liu, 2019; Torre et al, 2015). The oldest-old represent an adequate model of human longevity to study the adverse effects of progressive aging on cancer (Nolen et al, 2017). Longevous individuals present genetic variants associated with cancer susceptibility, and their phenotype manifestation might depend on their ancestry (Aizer et al, 2014; Jin et al, 2016; Özdemir and Dotto, 2017). It is well-established in literature that socio-economic and biological differences can contribute to distinct cancer susceptibilities among human populations.
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