Digit ratio (2D:4D) in women and men with lung cancer

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. Among both women and men, lung cancer is the leading cause of cancer death and in most nations, it is the most frequent neoplasm among men 1,2. The incidence of lung cancer is both age-and sex-dependent. With regard to age, rates are low in people younger than 40 years but with increases up to the age of 75-80 years. However, with regard to sex, lung cancer rates have tended to show a decline in men but an increase among women. An important causal factor in these patterns is smoking practices 3-5. The comparisons between those that smoke and never-smokers regularly show 20 to 50-fold increases in risk for the former. Moreover, duration of smoking is a strong correlate of lung cancer risk 6 and sex dependent changes in mortality reflects changes in rates of smoking among age-cohorts of women and men 7,8. However, there are risk factors other than smoking and these include various single nucleotide polymorphisms, family history, diet, alcohol, chronic lung diseases, occupational factors, air pollution and hormonal factors 9-13. With regard to hormonal factors, postnatal effects of endogenous sex steroids may have an influence on lung cancer risk. Receptors for oestrogen and progesterone are expressed in lung cells, of both normal and lung cancer lines. 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 cells 14,15. Local production of oestrogens in the lung, either by lung cells or by infiltrating macrophages and other inflammatory cells, may be a significant source of oestrogen that could drive the tumour process, i...

Association of Digit Ratio With Depression and Hopelessness in Females

“…earlier onset of the disease in women. 11 Also, the right and left hands 2D:4D have been reported to be higher in the women with the breast cancer. 12 In men with higher 2D:4D, the neck circumference which is positively correlated with the factors of the metabolic syndrome, has been shown to be higher.…”

Prenatal oestrogen-testosterone balance as a risk factor of migraine in adults

“…Geschwind and Galaburda suggested that there is an association between prenatal testosterone migraine and left-handedness [34]. Masculinized 2D:4D has been associated in women with breast cancer [30], lung cancer [33], and carpal tunnel syndrome [51] and prostate cancer in men [52]. Feminized 2D:4D has been linked to heart disease in men [53] and greater pain resistance in women [54].…”

“…Δ2D:4D was first considered to be a correlate of prenatal sex steroids by Manning et al [28] and further by Manning & Peters in studies concerned with handedness [29]. The 2D:4D digit ratio seems to be the risk factor of many diseases in different populations, among others with breast cancer [30], coronary heart disease [31], ischemic stroke [32] and lung cancer [33]. Geschwind and Galaburda (1985) were the first who hypothesised that prenatal testosterone slows down the growth of certain areas of the left hemisphere and promotes the growth of the homologous areas of the right hemisphere.…”

Can Digit Ratio (2D:4D) Be Indicative of Predispositions to Autoimmune Thyroid Diseases in Women - Hashimoto Thyroiditis and Graves’ Disease?

“…In addition, right 2D:4D is often found to be lower than left 2D:4D suggesting the former is more sensitive to prenatal sex steroids ( 18 ). Thus, high Δ r-l 2D:4D (right – left 2D:4D) is also thought to indicate high prenatal estrogen and low prenatal testosterone ( 19 , 21 ). Studies analyzing digit development in an animal model in mice confirmed this hypothesis and showed that 2D:4D depends on the androgen and estrogen receptors situated mainly in the ring finger and also in the index finger ( 22 ).…”