Digital biomarker 2D:4D as a predictor of cancer: A systematic review.

Background: The digital ratio between the second and fourth digits of the hands, known as 2D:4D, is sexually dimorphic. It has been suggested that a low 2D:4D indicates high exposure to prenatal testosterone and low estrogen exposure while a high 2D:4D indicates the inverse. The 2D:4D may be predictive of cancer susceptibility, and this may be particularly true in cancers that show differences between sexes in their occurrence.

Aim: To conduct a systematic review of published epidemiological literature examining the association between 2D:4D and cancer.

Method: This review was carried out according to criteria recommended for the systematic review of Statement PRISMA. We enrolled 25 papers involving eleven cancer topographies with 4,569 cases and 19,416 controls from Europe, America, Asia and Australia.

Results: We noticed variations and discrepancies in the results of the association between 2D:4D and cancer among the studies, either in those that had evaluated the same or different types of cancer, or in the same or distinct lateralities. However, a high 2D:4D was considered a likely predictor of cancer risk in 11 of 25 studies, a low 2D:4D was suggested as a predictor of risk in eight papers, and five of the twenty-five studies did not demonstrate any association.

Conclusions: Although this biomarker has the advantage of being easy to measure, it is noted that its relationship with sex hormone levels at specific stages of life has not yet been well quantified, and it has still been questioned. Hence, it is suggested that those findings from studies involving 2D:4D as a proxy for foetal hormone exposure should be interpreted with caution, as well as those studies which claim its association with cancer. Thus, this review shows the need for a greater number of epidemiological studies using more homogeneous methodology and techniques to better investigate the strength of the findings.