OBJECTIVES: Lynch syndrome (LS), occurring in about 1 in 279 people, is among the most common hereditary cancer syndromes. LS is associated with increased risk of a variety of cancers, including colorectal, endometrial, ovarian, stomach, urinary tract, and pancreatic, among others. Evidence linking LS with most cutaneous malignancies is lacking, although a topic of current research interest. The objective of this study was to determine the statistical strength of association of LS with various skin cancers.

METHODS: A retrospective analysis of U.S. claims data (2015-2022) was conducted using Merative™ MarketScan® Treatment Pathways. Prevalence of skin cancer (ICD-9/ICD-10 diagnoses) was compared between patients with tests (CPT codes) and diagnoses (ICD-9/ICD-10) indicating probable LS and patients without LS. Strength of association between LS and skin cancer was evaluated using odds ratios (OR) with 95% confidence intervals (95%CI).

RESULTS: We identified 2,038 patients with probable LS (“LS Cohort”) and 5,262,738 patients without LS (“Control Cohort”). Large differences in skin cancer prevalence were found between cohorts, corresponding with significantly (p<0.0001) strong association between LS and all skin cancer types. Prevalence of “any skin cancer” was 9.57% (LS Cohort) vs. 1.79% (Control Cohort; OR = 5.81, 95%CI [5.01, 6.74]). The strongest association was for malignant melanoma: 1.52% (LS Cohort) vs. 0.18% (Control Cohort; OR = 8.52, 95%CI [5.97, 12.16]). Statistically significant results for association were also found for squamous and basal cell carcinomas and other/unspecified skin cancers.

CONCLUSIONS: This study demonstrates the value and power of retrospective claims data for conducting exploratory epidemiology studies in diseases that are not well understood. Results show a significantly strong association of LS with skin cancers. With LS being a CDC “Tier 1” genomic condition, consideration should be given to add skin cancer screening to the roster of other cancer screenings for LS patients.