Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

Abstract

Background Obesity is prevalent in PR and has been associated with prostate cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) rs9930506 and rs9939609 in the FTO gene have been associated with both obesity and PCa. The aim of this work was to ascertain whether the presence of these SNPs is associated with PCa risk and severity in a cohort of Puerto Rican men. Methods and findings The study population consisted of 513 Puerto Rican men age ranging from 40–79 years old who underwent radical prostatectomy (RP) as the first treatment for PCa and 128 healthy Puerto Rican men age ranging from 40–79 years old. Genomic DNA (gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was defined based on RP stage and Gleason Score. The relationship of FTO SNPs with demographic, clinical characteristics, PCa status and PCa severity were assessed. Logistic regression models with a 95% confidence interval (CI) determined SNPs interaction with PCa risk and severity odds ratio (ORs). Results and discussion BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was present for both SNPs. The heterozygous forms (A/G; T/A) were the most prevalent genotypes and the frequency of alleles and genotypes for both SNPs agreed with those published in 1000 genomes. Results suggest an inverse association between the mutated rs9939609 and the risk of having PCa (OR: 0.53, 95% CI: 0.31–0.92) and a positive association with overweight (OR: 1.05, 95% CI: 0.68–1.62). Importantly, among the cases that were overweight, those with mutated rs9939609 had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84–2.32) although these results were not statistical significant upon adjustment. Limitations of the study were the relatively small cohort and lack of access to the weight history of all our subjects. Conclusion Results offer a research line to be followed with an expanded number of subjects that may provide a better statistical significance, to unravel the high mortality rate in this population.

Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer: A Population-Based Case-Control Study and Meta-Analysis

“…Although the association of the FTO rs9939609 polymorphism with PCa risk was weak in all previous studies, and might depend on different confounding factors, the meta-analysis performed in this study confirmed a strong and consistent association of this intronic variant with a decreased risk of PCa. A recent study also demonstrated that the association of the FTO rs9939609 SNP with a decreased risk of PCa was found in non-European populations, and that the presence of this genetic marker tended to be associated with disease severity in patients that were overweighted [89]. These findings, together with the lack of significant results in our functional studies, suggest that the role of the FTO locus in determining PCa might be mediated by complex obesogenic and/or diabetogenic mechanisms.…”

<p>The Potential Role of N6-Methyladenosine (m6A) Demethylase Fat Mass and Obesity-Associated Gene (FTO) in Human Cancers</p>

“…Interestingly, FTO rs9939609, which was a SNP known to be associated with obesity, was inversely related with low-grade prostate cancer risk, but positively related with high-grade prostate cancer. Salgado-Montilla et al 30 also discovered the same correlation between FTO rs9939609 and prostate cancer risk; nonetheless, the result was not statistically significant upon adjustment.…”

An integrated model of FTO and METTL3 expression that predicts prognosis in lung squamous cell carcinoma patients

“…Single-nucleotide polymorphisms (SNPs) in FTO was identified and not associated with body mass index (BMI), but was associated with melanoma risk in the first report in 2013 (21). However, it has been reported that rs9939609 polymorphism in the FTO gene is associated with a risk of breast and prostate cancer (22). Both genetic changes and FTO expression are thought to be involved in the biological process of cancer.…”