Genetic Variation in the Transforming Growth Factor-β-Signaling Pathway, Lifestyle Factors, and Risk of Colon or Rectal Cancer

Abstract

Background The transforming-growth-factor-β-signaling pathway has been identified as being involved in colorectal cancer. Objective To determine how diet and lifestyle factors in combination with genetic variation in the transforming-growth-factor-β-signaling pathway alters colorectal cancer risk. Design We use data from two population-based case-control studies. Patients Participants included colon cancer cases (n=1574) and controls (1970) and rectal cancer cases (n=791) and controls (999). Main Outcome Measures Newly diagnosed cases of colon or rectal cancer. Results Colon and rectal cancer risk increased with the number of at-risk genotypes within the transforming-growth-factor-β-signaling pathway (odds ratio 3.68 95% confidence interval 2.74,4.94 for colon cancer and odds ratio 3.89, 95% confidence interval 2.66,5.69 for rectal cancer). A high at-risk lifestyle score also resulted in significant increased risk with number of at-risk lifestyle factors (odds ratio 2.99 95% confidence interval 2.32,3.85 for colon cancer and odds ratio 3.37 95% confidence interval 2.24,5.07 for rectal cancer). The combination of high-risk genotype and high-risk lifestyle results in the greatest increase in risk (odds ratio 7.89 95% confidence interval 4.45,13.96 for colon cancer; odds ratio 8.75 95% confidence interval 3.66,20.89 for rectal cancer). Limitations Results need validation in other large studies of colon and rectal cancer. Conclusions In summary, our data suggest that there is increased colon and rectal cancer risk with increasing number of at-risk genotypes and at-risk lifestyle factors. While the integrity of the pathway can be diminished by number of high-risk genotypes, this risk can be in part offset by maintaining a healthy lifestyle.

Genetic variants in the TGFβ-signaling pathway influence expression of miRNAs in colon and rectal normal mucosa and tumor tissue

“…As we have previously shown [4] several SNPs associated with genes in this pathway interact with each other and with lifestyle factors to alter risk of colorectal cancer. Thus, this is a complex pathway.…”

“…These SNPs were previously shown to be associated with colon and rectal cancer risk [4, 6, 7]. eIF4E is essential for ribosomal recruitment and the initiation of translation [33]; eIF4E binds eIF4A and eIF4G to form the eIF4F complex that binds target mRNAs.…”

A systematic SNP selection approach to identify mechanisms underlying disease aetiology: linking height to post-menopausal breast and colorectal cancer risk

“…SNPs in TGF-β signalling pathway genes have been associated with increased breast cancer risk35. Moreover, it has been found that a high number of at-risk variants in genes in the TGF-β signalling pathway increased the risk of colon and rectal cancer36. That cross-talks between Ihh and TGF-β signalling pathways are important in linking height to cancer, is likely when considering other complex diseases such as coronary artery disease (CAD).…”

There Will Be a “Surgeromics” In Our Future? Where the Relationship between Technological Innovation and Knowledge and Surgery is Leading Us

“…Indeed the research conducted so far, evidence of a difference in risk of cancer depending on the presence of some SNPs: in particular, in the context of neoplastic disease of the Colon and Rectum in the last decade there have been important and significant developments that have led to the identification of several SNPs and Signaling Pathways whose activity is closely linked to the onset, development, progression and metastasis of cancer [13][14] , as they are understanding some of the features of therapeutic effectiveness depending on the presence or absence of particular SNPs or specific combined oncogenic pathways [15] : to date, we can talk about of SNPs able to affect increase or decrease of the risk of getting cancer or the efficacy of specific pharmacological treatments [16][17][18] . Tremblay et al refer that, currently,10% of marketed medications propose or recommend genetic testing for optimal treatment [1] .…”