Genetic Contribution to Non-Squamous, Non-Small Cell Lung Cancer in Non-Smokers
Shamus R. Carr1, Wallace Akerley2, Mia Hashibe2, Lisa A. Cannon-Albright2, 1University of Maryland School of Medicine, Baltimore, MD, USA, 2University of Utah, Salt Lake City, UT
OBJECTIVE: Lung cancer demonstrates significant excess relatedness for both close and distant relationships. This provides strong evidence for both environmental and more importantly genetic contributions. It is not known if the heritable contribution varies by histology for lung cancer.
METHODS: We analyzed a population-based computerized genealogy resource linked to a statewide cancer registry of lung cancer cases (n=5,408) for evidence of a genetic contribution based upon specific histology. Cases were grouped by histology (carcinoid, small cell, and non-small cell). Non-small cell lung cancer was further broken into subtypes. The genealogical index of familiality test (GIF) was used. This tests for excess pairwise relatedness of familial clustering and is used to consider the average relatedness measure by comparing 1,000 sets of matched controls to the cases. This test was also performed while ignoring for close, less then first cousins, relationships (dGIF).
RESULTS: Significant excess relatedness was observed for all lung cancer cases regardless of histology (p<0.001); this supports a genetic contribution. Only non-small cell lung cancers remained significant when all pairwise relationships were considered (p=0.005). When stratified by smoking status, only non-smoking-related, non-squamous lung cancer remained significant for both close and distant relations (p=0.043).
CONCLUSIONS: Non-squamous cell carcinoma shows significant excess relatedness, even when close relationships are ignored only in non-smokers. This provides strong evidence for a genetic contribution in addition to the recognized environmental contribution. These findings were not observed for other histologies, for which the observed relatedness of cases did not differ from expected relatedness.