Background: World Trade Center (WTC) responders were exposed to a complex mixture of carcinogens during rescue, recovery, and cleanup operations on and after September 11th, 2001. Elevated rates of several primary cancers have been documented among WTC responders, and prior work has demonstrated long-term upregulation of inflammatory genes and pathways related to WTC exposure. Although multiple primary cancers are uncommon in the general population, WTC responders may be at increased risk, yet the burden of multiple primary cancers in this population remains underexplored
Objectives: The objective of this study was to evaluate the relative occurrence of multiple primary cancers among male WTC general responders compared with a large, population-based cohort of male cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database.
Methods: We assembled a cohort of male WTC general responders enrolled in the WTC Health Program with at least one certified primary cancer from 2002 through 2022. These individuals were compared with male cancer patients aged ≥20 years from 17 SEER registries diagnosed during the same period. Non-melanoma skin and unclassifiable cancers were excluded. Multiple primary cancer status was defined as having two or more distinct cancer types. Repeated cancers in the same organ/sites were counted as a single primary cancer in both cohorts. Crude and age-standardized proportion ratios (PRs) with 95% confidence intervals (CIs) were calculated using the 2000 U.S. standard population.
Results: The analysis included 4,815 male WTC responders and 3,376,402 male SEER cancer patients. Overall, 527 WTC patients (10.9%) had multiple primary cancers, compared with 353,384 SEER patients (10.5%). The crude PR was 1.05, while the age-standardized PR was 1.84 (95% CI: 1.61-2.11). Age-specific analyses showed the highest relative burden among younger responders, with PRs of 3.76 (95% CI: 3.04-4.67) for ages 20-44 and 1.36 (95% CI: 1.17-1.58) for ages 45-54 years. The 55-64 year group showed little differences (PR = 1.02; 95% CI: 0.89-1.15), whereas responders aged ≥65 years had a lower proportion of multiple primary cancers than SEER patients (PR = 0.79; 95% CI: 0.65-0.96). Age-adjusted PRs were elevated among White patients (PR = 1.99; 95% CI: 1.71-2.31) and patients categorized as other race (PR = 3.26; 95% CI: 1.96-5.41). Among first/second primary cancer sequences, thyroid/prostate, prostate/thyroid, and melanoma/prostate combinations were proportionally more common in WTC responders than in SEER.  
 
Conclusion: Male WTC responders experience a significantly higher burden of multiple primary cancers compared with the general U.S. cancer population, particularly among responders diagnosed at younger ages. These findings support multiple primary cancers as an important, previously underrecognized outcome of WTC exposure. Looking forward, enhanced cancer surveillance and monitoring strategies may be warranted for WTC responders and similarly exposed populations.

Relative Rate of Multiple Primaries by Age at Diagnosis