Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer

Abstract

Summary 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.

Ongoing cancer burden after a diagnosis of cutaneous squamous cell carcinoma

“…Importantly, these new results 6 again highlight that SCC should be considered a consequential disease. SCC carries a clearly increased burden of morbidity and mortality due to patients subsequently experiencing a higher than expected incidence of both skin and nonskin cancers, with the findings from this study providing some evidence suggesting that this propensity may be more pronounced in those with a relevant family history.…”

“…4,5 Risk models incorporating genetic risk using polygenic risk scores or the number of risk alleles in KC development showed improved discriminative ability. 6,7 Despite the increased risk for developing KC in patients with AK, a risk prediction model for KC that is developed among those with AK lesions has been lacking.…”

“…5 In this issue of the BJD, Chattopadhyay and colleagues provide further insights. 6 They used the population-based Swedish Family Cancer Database to examine the influence of family history on second primary cancers following a diagnosis of SCC. This database has the advantage of including data on both invasive and in situ SCC, along with population-wide unique identifiers, enabling complete assessment of family history since the inception of the database in 1958.…”

“…In this issue of the BJD , Chattopadhyay and colleagues provide further insights . They used the population‐based Swedish Family Cancer Database to examine the influence of family history on second primary cancers following a diagnosis of SCC.…”

Familial risks between giant cell arteritis and Takayasu arteritis and other autoimmune diseases in the population of Sweden

“…Methods used were in principle similar to those in our previous family studies on cancer and autoimmune diseases [13][14][15] . We identified AID patients from the Swedish Hospital Discharge Register (years 1964 through 2012, full national coverage from 1986 onwards) and the Outpatient Register (2001 through 2012).…”