Thus, if fetal development of mammary glands is linked to predisposition to adult breast cancer then 2D : 4D might be an indicator of this disease predisposition. Among these, there are three genes ( Wnts, Fgfs, and FGFR1) that influence Tbx genes, which initiates mammary gland formation ( Eblaghie et al, 2004). During the development of 2D : 4D, there are at least 19 skeletogenic genes that are activated or deactivated by prenatal testosterone and oestrogen ( Zheng and Cohn, 2011). Furthermore, there is evidence from mouse models that the sex hormones and genes involved in the differentiation of fetal 2D : 4D may also be involved in mammary gland initiation. Recent evidence from a mouse model suggests that 2D : 4D depends critically on in utero exposure to androgens relative to oestrogen exposure, with higher testosterone relative to oestrogen leading to lower right 2D : 4D ( Zheng and Cohn, 2011). Several lines of evidence indicate that prenatal testosterone exposure, or underlying sensitivity to testosterone, is inversely related to 2D : 4D, especially right 2D : 4D, as well as being inversely related to the difference between right and left 2D : 4D (Δ r−l) ( McIntyre, 2006 Breedlove, 2010). Contemporary anthropological studies have found small but consistent sex differences in 2D : 4D, with men having lower average 2D : 4D than women ( Manning et al, 1998 McIntyre, 2006 Hönekopp and Watson, 2010). The investigation of digit ratios as possible markers of androgen action in early life began with the long-recognised observation that, compared with women, adult males tend to have longer ring fingers relative to other fingers. The ratio of the lengths of the index (2D) and ring (4D) fingers, expressed as the ratio 2D : 4D, has been proposed as a marker of prenatal androgen action or sensitivity to androgens. The potential importance of cumulative or critical exposure to sex hormones has led to consideration of in utero hormone factors that might influence later risk of breast cancer. Additionally, many well-established risk factors for breast cancer such as age at menarche, age at menopause, hormone replacement therapy use, and duration of lactation can be considered measures of cumulative exposure to oestrogen that the breast epithelium is exposed to over time ( Henderson and Feigelson, 2000). Prospective studies have consistently reported that higher levels of endogenous oestrogens and androgens, and lower levels of sex hormone binding globulin (SHBG) are associated with risk of post-menopausal breast cancer ( Key et al, 2002 Manjer et al, 2003 Missmer et al, 2004 Zeleniuch-Jacquotte et al, 2004 Kaaks et al, 2005b Hankinson and Eliassen, 2007 Baglietto et al, 2010), and there is some evidence indicating similar associations with pre-menopausal breast cancer risk as well ( Kaaks et al, 2005a Eliassen et al, 2006). There is substantial evidence implicating androgens and oestrogens in the aetiology of breast cancer. If confirmed in other studies, this suggests that lower exposure or sensitivity to prenatal testosterone might be associated with lower risk of breast cancer. Conclusion:ĭigit ratio measures might be associated with breast cancer risk and age at onset of breast cancer. We also observed associations between both right 2D : 4D and Δ r−l and age at menopause, with increasing digit ratio measures related to earlier mean age at menopause. Among breast cancer cases, both right 2D : 4D and Δ r−l were inversely associated with age at diagnosis. We found a direct association between left 2D : 4D and breast cancer risk, an inverse association between Δ r−l and risk of breast cancer, but no association between right 2D : 4D and breast cancer risk. Hazard ratios (HR) and 95% confidence intervals (CI) for a one standard deviation difference in 2D : 4D measures were obtained from Weibull survival models, and linear regression models were used to examine potential associations between 2D : 4D measures and age at menarche and menopause. ![]() ![]() Of the 9044 women with available data, we identified 573 incident breast cancer cases. We derived the ratio of the lengths of the index and ring fingers (2D : 4D), and right minus left 2D : 4D (Δ r−l) from digit lengths measured from photocopies of participants’ hands collected during a recent follow-up of the Melbourne Collaborative Cohort Study, a prospective study including 24 469 women. We aimed to assess whether 2D : 4D measures are associated with breast cancer risk.
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