Abstract
A prenatal sex steroid environment of high prenatal testosterone and low prenatal oestrogen inhibits lung development and may predispose individuals to be vulnerable to lung disease in later life. Therefore, the aim of this report was to investigate whether there is an association between right and left 2D:4D (biomarker of prenatal sex steroids exposure) and primary lung cancer in women and men. Also, we considered the relationship between right–left 2D:4D (Δ2D:4D, a negative correlate of high prenatal testosterone and low prenatal oestrogen) and the age of lung cancer diagnosis. The study included 109 patients (61 men) with lung cancer and 197 controls (78 men). In the study we found that: (i) women with lung cancer have lower 2D:4D compared to controls (the effect was independent of smoking), (ii) among women with cancer, age at diagnosis was positively related to 2D:4D, i.e. women with masculinized 2D:4D present earlier with the cancer than women with feminized 2D:4D, (iii) among men with lung cancer, those with the most aggressive form (small-cell lung cancer) had masculinized (low) Δ2D:4D compared to those with the less aggressive form (non-small cell lung cancer). The data suggests that masculinized right 2D:4D and Δ2D:4D are associated with a predisposition to lung cancer and/or the more aggressive forms of lung cancer.
Highlights
A prenatal sex steroid environment of high prenatal testosterone and low prenatal oestrogen inhibits lung development and may predispose individuals to be vulnerable to lung disease in later life
Concerning prenatal sex steroids influence on lung development, different expression of oestrogen receptors β (ERβ) mRNA compared to oestrogen receptors α (ERα) mRNA was found in human lung tissue during foetal d evelopment[24]
Manning et al have suggested that 2D:4D is a biomarker of prenatal sex steroids exposure—low 2D:4D correlates with high prenatal testosterone and low oestrogens, while high 2D:4D results from low foetal testosterone and high oestrogens[26,27,28]
Summary
A prenatal sex steroid environment of high prenatal testosterone and low prenatal oestrogen inhibits lung development and may predispose individuals to be vulnerable to lung disease in later life. The aim of this report was to investigate whether there is an association between right and left 2D:4D (biomarker of prenatal sex steroids exposure) and primary lung cancer in women and men. We considered the relationship between right–left 2D:4D (Δ2D:4D, a negative correlate of high prenatal testosterone and low prenatal oestrogen) and the age of lung cancer diagnosis. With regard to hormonal factors, postnatal effects of endogenous sex steroids may have an influence on lung cancer risk. Oestradiol causes proliferation of lung cancer cells as do combinations of oestrogen and progesterone The latter combination facilitates secretion of vascular endothelial growth factors and increases numbers of progenitor tumour c ells[14,15]. Experimental evidence for the suggestions of Manning et al have been reported in mouse models by Zheng and Cohn and in rats by Auger et al They found that sex differences in 2D:4D (males < females) are determined by a balance of prenatal testosterone to oestrogen in a narrow time window of foetal digit d evelopment[31,32]
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