The role of fetal programming in human carcinogenesis - May the Barker hypothesis explain interindividual variability in susceptibility to cancer insurgence and progression?

Coghe F.

First

Writing - Original Draft Preparation

;Fanni D.

Writing - Original Draft Preparation

;Gerosa C.

Writing - Original Draft Preparation

;Ravarino A.;Mureddu M.;Cerrone G.;Coni P.;Pichiri G.;Congiu T.;Piras M.;Cau F.

Writing - Review & Editing

;Aimola V.;Balestrieri A.;Lai E.;Manchia M.

Writing - Review & Editing

;Scano A.;Orru G.;La Nasa G.

Writing - Review & Editing

;Van Eyken P.;Saba L.

Writing - Review & Editing

;Scartozzi M.

Writing - Review & Editing

;Castagnola M.

Writing - Review & Editing

;Faa G.

Writing - Original Draft Preparation

2022-01-01

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Abstract

The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.