BackgroundHealthy aging perceives human longevity probably due to carrying the defensive genes. Forkhead box O (FOXO) transcription factors provide the most convincing example of a conserved genetic pathway at the point between aging and cancer. This pilot study was performed to examine the single nucleotide variants rs2253310 and rs4946936 of the Forkhead box O 3 (FOXO3 gene) in octogenarians and gastrointestinal tract (GIT) cancer patients in the north Indian population.Main bodyIn silico mutational analysis of the FOXO3 gene in 25 participants. Two single nucleotide variants (SNVs) g.7556C>G (rs2253310) heterozygous and g.122284T>C (rs4946936) homozygous observed and reported previously. However, there is a common association of these SNVs in different ethnic groups. No significant differences in the genotype and allele frequencies for the study groups observed.Short conclusionThis study observes two single nucleotide variants, g.7556C>G (rs2253310) and g.122284T>C (rs4946936), of the FOXO3 gene in the study groups which influence human longevity. Longevity-associated FOXO3 variants may be associated with GIT cancer in the north Indian population. As a result, looking for genes linked to longevity will lead to discovering new cancer targets. Further studies with a large population are necessary to elucidate the role of the FOXO3 gene in octogenarians.