The Association of Digit Ratio (2D : 4D) with Cancer: A Systematic Review and Meta-Analysis

OBJECTIVE: Intrauterine sex hormone environment as indicated by the second to the fourth digit ratio (2D : 4D) can be associated with cancer risk. This systematic review and meta-analysis aimed to evaluate the association of 2D : 4D with cancer diagnosis, malignancy, and age at presentation. METHODS: Studies that evaluated the association of 2D : 4D with cancer risk were collected from Pubmed/MEDLINE and Clarivate Analytics databases. Nineteen studies were included in the qualitative analysis. RESULTS: The 2D : 4D ratio was studied in prostate cancer, breast cancer, testicular cancer, gastric cancer, oral cancer, brain tumors, and cervical intraepithelial neoplasia. Low 2D : 4D was associated with prostate cancer, gastric cancer, and brain tumors, while high 2D : 4D, with breast cancer risk and cervical dysplasia. The 2D : 4D ratio was not associated with prostate, breast, and gastric cancer stage. Greater 2D : 4D ratio was associated with younger presentation of breast cancer and brain tumors. The meta-analyses demonstrated that testicular cancer was not associated with right-hand 2D : 4D ratio (p = 0.74) and gastric cancer was not associated with right-hand (p = 0.15) and left-hand (p = 0.95) 2D : 4D ratio. CONCLUSIONS: Sex hormone environment during early development is associated with cancer risk later in life. Further studies exploring the link between intrauterine hormone environment and cancer risk are encouraged.