Familial Risks and Mortality in Second Primary Cancers in Melanoma

Background: Malignant melanoma (MM) patients are at increasing risk of developing second primary cancers (SPCs). We assessed mortality and risk of SPCs in MM patients with siblings or parents affected with same cancer compared with that of the general population. Methods: We used the Swedish Family-Cancer Database to assess relative risks (RRs) and causes of death in SPCs until 2015 in patients with a MM diagnosis between 1958 and 2015. We identified 35 451patients with MM among whom 3212 received a subsequent diagnosis of SPC. RRs of SPCs after MM diagnosis were calculated stratifying over concordant family history of cancer in first-degree relatives. Results: Familial RRs were increased for second melanoma (RR = 19.28, 95% CI = 16.71 to 22.25), squamous cell skin cancer (RR = 7.58, 95% CI = 5.57 to 10.29), leukemia (RR = 5.69, 95% CI = 2.96 to 10.94), bladder (RR = 4.15, 95% CI = 2.50 to 6.89), ovarian (RR = 3.89, 95% CI = 1.46 to 10.37), kidney cancer (RR = 3.77, 95% CI = 1.57 to 9.06), cancer of unknown primary (RR = 3.67, 95% CI = 1.65 to 8.16), nervous system (RR = 2.88, 95% CI = 1.20 to 6.93), breast (RR = 2.34, 95% CI = 1.92 to 2.84), lung (RR = 2.24, 95% CI = 1.50 to 3.35), and prostate cancer (RR = 2.22, 95% CI = 1.89 to 2.61) with statistical significance. For all cancers, familial RR was in excess (2.09, 95% CI = 2.02 to 2.16 vs 1.78, 95% CI = 1.69 to 1.87; P_trend < .0001). Cause of death in MM patients with SPC is shown to be dependent on the cancer site though SPCs contributed to majority of deaths. Conclusions: SPCs appear higher with prior family history of cancer and contribute to mortality. SPC was the most common cause of death in patients with SPC and is almost uniformly the major contributing cause of death for all cancer sites. For improved survival in MM patients, prevention and early detection of SPCs would be important.