Risk of second primary cancers after malignant mesothelioma and vice versa

• First population-based study on risk of specific SPCs after malignant mesothelioma.
• Using the approach of bidirectional analyses of second cancers after first cancer.
• Using large high-quality Swedish FCD and including large samples of MM patients.
• The bidirectional association of pleural MM with kidney cancer suggests BAP1 gene.
• We found a bidirectional association of pleural MM with unknown primary cancer.

We aimed at investigating risk of specific second primary cancers (SPCs) after malignant mesothelioma (MM) and vice versa, which has not been reported. Among survivors of 3672 pleural MM and 895 peritoneal MM, overall 113 and 28 SPCs were recorded, respectively, while reverse analyses included overall 431 pleural and 88 peritoneal MMs after any first cancers. We found a bidirectional association of pleural MM with kidney cancer for overall [for second kidney cancer after pleural MM: standardized incidence ratios (SIRs) = 4.4, 95% confidence intervals (CIs): 2.0–8.3; for second pleural MM after kidney cancer: 2.3 (1.3–3.9)] and for <1 year follow-up [5.4 (2.0–12) and 4.9 (2.0–10), respectively, according to the 2-way analyses]. In contrast, a bidirectional association of pleural MM with unknown primary cancer was found only for follow-up ≥1 year [3.9 (1.1–10) and 2.8 (1.3–5.1), respectively]. We found a bidirectional association of pleural MM with kidney cancer for overall and for <1 year follow-up, suggesting the involvement of germline BAP1 mutations and increased medical surveillance, while the bidirectional association of pleural MM with unknown primary cancer suggests shared genetic or environmental risk factors.