BACKGROUND: Patients with squamous cell skin cancer (SCC) have an excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in patients with SCC is not known. OBJECTIVES: To quantify the risk of family history on SPCs in patients with SCC and estimate survival probabilities of patients with SPCs depending on family history. METHODS: With 13 945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios (HRs) were assessed using a multivariable Cox proportional-hazards model. RESULTS: Family history of invasive SCC increased risk of second invasive SCC [RR = 42·92, 95% confidence interval (CI) 33·69-50·32] compared with risk without family history (RR 19·12, 95% CI 17·88-21·08). Family history of any nonskin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC (RRFH = 1·48, 95% CI 1·35-1·61 vs. RRno FH = 1·40, 95% CI 1·32-1·48); significant increases were observed for seven different nonskin cancers. Most results were replicated for in situ SCC. SPC was deleterious for survival irrespective of family history; HR for patients with SPC was 4·28 (95% CI 3·83-4·72) vs. those without SPC (1·04). CONCLUSIONS: Family history of nonskin cancer was associated with approximately a doubling of risk for SPCs in patients with SCC. SPC increases the death rate in patients with SCC 3-4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs. What's already known about this topic? Second primary cancers (SPCs) are frequently diagnosed in patients with invasive and in situ squamous cell carcinoma (SCC); some epidemiological studies suggest a link to immune dysfunction. Family history of cancer is a risk factor for practically all first primary cancers but whether it also influences risk of SPCs in patients with SCC is not known. The possible influence of family history on survival in patients with SCC remains to be established. Linked Comment: Youlden and Baade. Br J Dermatol 2020; 183:414-415.

Cancer Gene Therapy Group Translational Immunology Research Program University of Helsinki Helsinki Finland

Center for Community based Healthcare Research and Education Department of Functional Pathology School of Medicine Shimane University Japan

Center for Primary Health Care Research Lund University 205 02 Malmö Sweden

Department of Family Medicine and Community Health Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY U S A

Division of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld 580 D 69120 Heidelberg Germany

Division of Molecular Genetic Epidemiology German Cancer Research Center Im Neuenheimer Feld 580 D 69120 Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany

Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague 30605 Pilsen Czech Republic

Faculty of Medicine University of Heidelberg Heidelberg Germany

Helsinki University Hospital Comprehensive Cancer Center Helsinki Finland

Hopp Children's Cancer Center Heidelberg Germany

Br J Dermatol. 2020 Sep;183(3):414-415. doi: 10.1111/bjd.18900. PubMed

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