Abstract
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.
Highlights
Cancer remains among the leading causes of death and disability worldwide [1]
The 2D : 4D ratio was studied in patients with prostate cancer (9 studies), breast cancer (2 studies), testicular cancer (2 studies), gastric cancer (2 studies), oral cancer (1 study), brain tumors (1 study), and cervical dysplasia (1 study)
Low 2D : 4D was associated with prostate cancer and brain tumors, while high 2D : 4D was associated with breast cancer and cervical dysplasia
Summary
Cancer remains among the leading causes of death and disability worldwide [1]. Global burden of cancer will continue to grow due to increasing age of expanding population [2]. Early identification of individuals at elevated cancer risk will become increasingly important for guiding targeted screening interventions and early diagnosis [3]. There is an increasing recognition that events and environment (including hormones) during in utero period when organs are still developing can increase cancer risk later in life [6, 7]. The 2D : 4D ratio is established during in utero period and is a stable signature of prenatal sex steroid exposure throughout life. Available evidence suggests that the 2D : 4D ratio is associated with behavioral, developmental, and somatic disorders and can have important health implications [12, 13]. Identification of 2D : 4D as cancer risk factor could potentially contribute towards earlier cancer diagnosis via targeted screening interventions of individuals who are at elevated cancer risk
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