Title: Shared heritability and functional enrichment across six solid cancers.
Authors: Jiang, Xia (see original citation for additional authors)
Published In Nat Commun, (2019 01 25)
Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
PubMed ID: 30683880
MeSH Terms: Breast Neoplasms/diagnosis; Breast Neoplasms/ethnology; Breast Neoplasms/genetics*; Breast Neoplasms/pathology; Case-Control Studies; Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/ethnology; Colorectal Neoplasms/genetics*; Colorectal Neoplasms/pathology; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Head and Neck Neoplasms/diagnosis; Head and Neck Neoplasms/ethnology; Head and Neck Neoplasms/genetics*; Head and Neck Neoplasms/pathology; Humans; Inheritance Patterns*; Lung Neoplasms/diagnosis; Lung Neoplasms/ethnology; Lung Neoplasms/genetics*; Lung Neoplasms/pathology; Male; Mental Disorders/ethnology; Mental Disorders/genetics; Mental Disorders/physiopathology; Neoplasm Proteins/genetics; Ovarian Neoplasms/diagnosis; Ovarian Neoplasms/ethnology; Ovarian Neoplasms/genetics*; Ovarian Neoplasms/pathology; Phenotype; Polymorphism, Single Nucleotide; Prostatic Neoplasms/diagnosis; Prostatic Neoplasms/ethnology; Prostatic Neoplasms/genetics*; Prostatic Neoplasms/pathology; Smoking/ethnology; Smoking/genetics; Smoking/physiopathology