Polydactyly and Risk of Cancer

Syndromic polydactyly is often associated with an increased cancer risk. However, limited data exist regarding nonsyndromic polydactyly and its associated risk of subsequent malignancy. Therefore, our purpose was to investigate differences in rates of both malignant and benign neoplasms among pediatric patients diagnosed with nonsyndromic polydactyly compared with matched controls.

The TriNetX US Collaborative Network database was queried using ICD-9 and ICD-10 codes to identify patients aged 10 and younger diagnosed with any form of polydactyly. Patients were then divided into 2 cohorts depending on their history of polydactyly. These cohorts were propensity-matched based on age, sex, race, ethnicity, and congenital malformation syndromes associated with both polydactyly and malignancy. Subsequent rates of cancer were compared between patients with and without polydactyly.

A total of 9,266,353 patients aged 10 and younger were identified, of which 16,478 (0.18%) were diagnosed with polydactyly. After 1:1 propensity matching, both cohorts included 14,361 patients. Mean follow-up was 73 months for the polydactyly cohort and 78 months for the control cohort. Overall, the polydactyly cohort had a significantly increased rate of any neoplasm (3.3% vs. 2.6%) and benign neoplasms (2.6% vs. 2.2%) compared with the control cohort. There was no significant difference between rates of malignant neoplasms between cohorts. In contrast, when analyzing site-specific cancer risk between cohorts, malignant neoplasms of bone or cartilage (0% vs. 0.1%) as well as breast (0% vs. 0.1%) were significantly higher in the control cohort compared with the polydactyly cohort. However, there were no significant differences between cohorts among rates of alternative site-specific cancers, including digestive, respiratory or intrathoracic, skin, mesothelial or soft tissue, urinary tract, central nervous system (CNS), thyroid or endocrine, neuroendocrine, lymphoid, and lip, oral cavity, or pharynx. Furthermore, after stratifying follow-up time periods, no significant differences were appreciated between polydactyly and control cohorts in rates of all neoplasms, malignant neoplasms, and benign neoplasms at follow-up <1 year, between 1 and 5 years, and >5 years.

Nonsyndromic polydactyly seems to be associated with increased rates of neoplasms, particularly benign neoplasms. However, site-specific cancers of bone, cartilage, and breast were significantly decreased in polydactyly patients. Although our large study further investigates this complex relationship, further studies are needed to elucidate polydactyly and its cancer implications.

Retrospective cohort study, level of evidence III.