Cancer is one of the leading cause of death in the world with the prevalence of >10 million mortalities annually. Current cancer treatments include surgical intervention, radiation, and taking chemotherapeutic drugs, which often kill the healthy cells and result in toxicity in patients. Therefore, researchers are looking for ways to be able to eliminate just cancerous cells. Intra-tumor heterogeneity of cancerous cells is the main obstacle on the way of an effective cancer treatment. However, better comprehension of molecular basis of tumor and the advent of new diagnostic technologies can help to improve the treatment of various cancers. Therefore, study of epigenetic changes, gene expression of cancerous cells and employing methods that enable us to correct or minimize these changes is critically important. In this paper, we will review the recent advanced strategies being used in the field of cancer research.
This study is the first to identify the effects of FTO genotype on the interactions between the level of macro-nutrients intake and the expression level of fat mass and obesity associated (FTO) and homeobox transcription factor iriquois-3 (IRX3) genes This longitudinal study was carried out on 84 overweight and obese adolescent boys in Tehran, Iran. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in PBMCs and macro-nutrients' intake were assessed at baseline and after 18 weeks of the intervention. The results identified that the higher carbohydrates intake significantly up-regulated the FTO gene (P = 0.001) and down-regulated the IRX3 gene (P = 0.01). Protein intake up-regulated the FTO gene (P = 0.001). In carriers of GG genotype of FTO gene, the amount of dietary carbohydrate had a positive association with FTO gene expression (p = 0.001, and p = 0.04, respectively). In AA/AG carriers, dietary protein was positively associated with FTO gene expression (p = 0.001) and dietary carbohydrate was negatively associated with IRX3 gene expression (P = 0.04). Therefore, dietary carbohydrateseems to be associated with FTO and IRX3 genes expression. These associations are influenced by FTO genotype.
Background
Lifestyle intervention may have a critical effect on the association between genetics and obesity. This study aimed to investigate changes in
FTO
and
IRX3
gene expression in obese and overweight male adolescents undergoing a lifestyle intervention and the role of
FTO
genotype in this interaction.
Methods
This study was a field trial of 62 adolescents from boys’ high schools in Tehran, Iran. Two schools were randomly allocated as the intervention (n = 30) and control (n = 32) schools. The rs9930506 SNP in
FTO
was genotyped at baseline and the level of
FTO
and
IRX3
expression in peripheral blood mononuclear cells (PBMCs). Anthropometric measurements were assessed at baseline and after 18 weeks of intensive lifestyle intervention.
Results
Our results showed that
IRX3
expression in the intervention group was significantly up-regulated compared to baseline (P = 0.007) and compared to the control group (P = 0.011).The intervention group had significantly up-regulated transcripts of
IRX3
only in rs9930506 risk allele carriers of the intervention group compared to risk allele carriers of the control group (P = 0.017). Moreover, our data showed that the FTO expression was up-regulated in AA genotype carriers and down-regulated in AG/GG genotype carriers (P = 0.017).
Conclusion
Lifestyle modification may exert its effects on obesity through changes in the expression level of the
FTO
and
IRX3
genes. However,
FTO
genotype plays a role in the extent of the effect of lifestyle changes on gene expression. Further studies are crucial to have a better understanding of the interaction between lifestyle, genetics and anthropometric measurements.
Trial registration
This paper reports a comprehensive intervention study (Interactions of Genetics, Lifestyle and Anthropometrics study or IGLA study), which is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. (
https://www.irct.ir/searchresult.php?id=25699&number=2
)
Electronic supplementary material
The online version of this article (10.1186/s12967-019-1921-4) contains supplementary material, which is available to authorized users.
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