Indexed on: 23 Oct '19Published on: 11 May '19Published in: Journal of Thoracic Oncology
Published risk estimates for diagnosis of lung cancer based on family history are typically focused on close relatives, rather than a more diverse or complete family history. This study provides estimates of RR for lung cancer based on comprehensive family history data obtained from a statewide Cancer Registry linked to a high quality genealogy data resource that is extensive and deep. The risk estimates presented avoid common recall, recruitment, ascertainment biases, and are based on an individual's (proband's) lung cancer family history constellation (pattern of lung cancer affected relatives); numerous constellations are explored. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry to estimate relative risk (RR) for lung cancer for an individual based upon their lung cancer family history. The family history data available for a proband included degree of relationship (first to third-degree), paternal or maternal family lung cancer history, number of lung cancer affected relatives and age at diagnosis of affected relatives. Over 1.3M probands with specific constellations of lung cancer were analyzed. To estimate RRs for lung cancer, the observed number of lung cancer cases among probands with a specific family history constellation was compared to the expected number using internal cohort-specific rates. 5,048 lung cancer cases were identified. Significantly elevated RR was observed for any number of lung-cancer-affected relatives among first-, second-, or third-degree relatives. RRs for lung cancer were significantly elevated for each additional lung cancer first-degree relative (FDR) ranging from RR=2.57 (2.39, 2.76) for >= 1 FDR to RR=4.24 (1.56, 9.23) for ≥3 FDRs affected. In an absence of FDR family history, increased risk for lung cancer was significant for increasing numbers of affected second-degree relatives (SDR) ranging from 1.41 (1.30, 1.52) for ≥ 1 SDR to 4.76(1.55, 11.11) for ≥ 4 SDRs. In the absence of affected FDRs and SDRs, there were significantly increased risks based upon lung cancer affected third-degree relatives (TDR) ranging from 1.18 (1.11, 1.24) for ≥1 affected TDR to 1.55 (1.03, 2.24) for ≥ 4 affected TDRs. RRs were significantly increased with earlier age at diagnosis of a first degree relative, and equivalent risks for maternal compared to paternal history were observed. This study provides population-based estimates of lung cancer risk based on a proband's complete family history (lung cancer constellation). Many individuals at 2-5+ times increased risk for lung cancer were identified. Estimates of RR for lung cancer based on family history are arguably very relevant clinically. The constellation RR estimates presented could serve in individual decision making to direct resource utilization for lung cancer screening, and could be pivotal in decision making for screening, treatment, and post treatment surveillance. Copyright © 2019. Published by Elsevier Inc.