A Linear Relationship between the Number of Cancers among First-degree Relatives and the Risk of Multiple Primary Cancers.

With advances in the early detection and treatment of cancer, the incidence of multiple primary cancers (MPC), or second primary cancers, has risen over time. Characterization of etiologic risk factors, including family history of cancer, within the general population is critical for assessing MPC risk in patients. We examined the association between family history of cancer among first-degree relatives and MPC risk in a prospective study of 139,958 participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI), adjusting for potential confounders. Over a median follow-up of 16 years (interquartile range: 11-19 years), 6,170 participants were diagnosed with MPC. Having a family history of cancer increased the risk of MPC by 18% (HR=1.18, 95%CI: 1.12-1.24). A positive linear trend was observed between the reported number of cancers in the family history and MPC risk with HRs (95%CI) of 1.13 (1.07-1.20), 1.23 (1.14-1.33), 1.29 (1.15-1.45), and 1.42 (1.20-1.70) for 1, 2, 3, and 4+ cancers among first-degree relatives, respectively (Ptrend=2.36x10-13). No significant differences were observed by cancer histology or specific types of cancer reported in the family history. Our study demonstrates that family history of cancer is an important risk factor for the development of multiple primary cancers and that a comprehensive of assessment of the number of cancers reported among first-degree relatives may identify those at higher risk who may benefit from targeted cancer prevention and screening strategies.