Second-To-Fourth Digit Ratio (2D:4D) in Breast Cancer: A Systematic Review.

The second-to-fourth digit ratio (2D:4D) is considered an indirect marker of prenatal sex hormone exposure and has been investigated as a potential indicator of susceptibility to hormone-related diseases, including breast cancer. The purpose of this systematic review is to evaluate the relationship between the 2D:4D finger ratio and breast cancer risk. This systematic review was conducted in accordance with the PRISMA 2020 statement. PubMed, Scopus, and Web of Science were searched without publication year restrictions. Eligible observational studies were selected using predefined PICOS criteria, and methodological quality was assessed using Joanna Briggs Institute critical appraisal checklists. Seven observational studies involving 13 556 women (2817 breast cancer cases and 10 739 controls) were included. Most case-control studies reported significantly higher right- and/or left-hand 2D:4D ratios among women with breast cancer than among healthy controls. However, the prospective cohort study reported an association only for the left-hand 2D:4D ratio, whereas the largest multicenter case-control study did not demonstrate a consistent overall association between right- or left-hand 2D:4D ratios and breast cancer risk. Overall, current findings suggest a possible association between higher 2D:4D ratios and breast cancer risk, although substantial heterogeneity exists across studies. This systematic review suggests that the 2D:4D finger ratio may be associated with breast cancer risk. However, substantial heterogeneity across studies warrants cautious interpretation, and further large prospective studies are needed to clarify its potential role in breast cancer risk assessment.