Endometrial and ovarian tumours are almost mechanistically affected by reproductive hormones. Ovarian cancer may be explained as metastatic or synchronous primary ovarian cancer, and the specific diagnosis is a challenge. This study aimed to investigate the mutations in fat mass and obesity-associated (FTO) genes and investigated the association of these mutations with the risk of endometrial and ovarian cancers as well as with cancer grade and stage. Blood samples were collected from 48 endometrial and ovarian cancer cases and 48 healthy women. Genomic DNA was extracted, and PCR was done to amplify FTO exons 4-9. Sanger sequencing identified 6 different novel mutations submitted to DDBJ: p.W278G and p.G284G in exon 4, p.S318I and p.A324G in exon 5 and two mutations in intron 4. Other mutations were also detected in FTO gene sequencing results, rs112997407 in intron 3, rs62033438, rs62033439, rs8048254 and rs8046502 in intron 4. The novel p.W278G, p.S318I and p.A324G mutations were predicted to be damaging. We did not find a significant association for all variables with cancer risk or clinical stage and grade except for rs62033438 variants, which showed a significant association with cancer grade, especially AA genotype (OR= 15, 95% CI:1.32 -169.88, P= 0.03). In conclusion, the statistical analysis did not clarify whether FTO mutations are implicated in cancer. Further studies with more samples are recommended to provide a more accurate picture of the correlation between FTO mutations and endometrial and ovarian cancer susceptibility.
Keywords: Endometrial cancer; FTO; Ovarian cancer; Screening.