Abstract :
Keywords Digit ratio; Cancer; Systematic review; 2d 4d Highlights * The ratio of the lengths of the index and ring fingers, 2D:4D, is often employed as marker of prenatal sex hormone exposure. * The 2D:4D may be considered a predictive biomarker for cancer risk, mainly in prostate, breast and gastric cancers. * The association between 2D:4D and cancer was evaluated in 25 papers involving eleven distinct topographies. * The 2D:4D has been claimed to be negatively correlated to prenatal testosterone exposure and positively to oestrogen. Abstract 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. Author Affiliation: (a) Health Science Program, State University of Montes Claros, Unimontes, Minas Gerais, Brazil (b) Medicine School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil (c) Dental School, State University of Montes Claros, Montes Claros, Minas Gerais, Brazil (d) Center for Rehabilitation of Craniofacial Anomalies, University of José Rosario Vellano, Alfenas, Minas Gerais, Brazil * Corresponding author at: Department of Clinical Medicine, Center of Biological and Health Sciences, State University of Montes Claros - Unimontes, Av. Prof. Rui Braga, s/n - Vila Mauriceia, Montes Claros, Minas Gerais, CEP 39408-354, Brazil. Article History: Received 25 January 2021; Revised 27 November 2021; Accepted 30 November 2021 Byline: Cláudia de A.D. Fonseca [claudia.fonseca@unimontes.br] (a,b,*), Daniella R.B. Martelli (c), Célia M.F. Maia (a), Verônica O. Dias (c), Adriana A. Carvalho (a,b), Hercílio Martelli Júnior (a,c,d)