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Whole Exome Sequencing of Highly Aggregated Lung Cancer Families Reveals Linked Loci for Increased Cancer Risk on Chromosomes 12q, 7p, and 4q
- Source :
- Cancer Epidemiol Biomarkers Prev
- Publication Year :
- 2020
- Publisher :
- American Association for Cancer Research (AACR), 2020.
-
Abstract
- Background: Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cancer. Methods: Parametric genetic linkage analysis was performed on these samples using two distinct analyses—the lung cancer only (LCO) analysis, where only patients with lung cancer were coded as affected, and the all aggregated cancers (AAC) analysis, where other cancers seen in the pedigree were coded as affected. Results: The AAC analysis yielded a genome-wide significant result at rs61943670 in POLR3B at 12q23.3. POLR3B has been implicated somatically in lung cancer, but this germline finding is novel and is a significant expression quantitative trait locus in lung tissue. Interesting genome-wide suggestive haplotypes were also found within individual families, particularly near SSPO at 7p36.1 in one family and a large linked haplotype spanning 4q21.3-28.3 in a different family. The 4q haplotype contains potential causal rare variants in DSPP at 4q22.1 and PTPN13 at 4q21.3. Conclusions: Regions on 12q, 7p, and 4q are linked to increased cancer risk in highly aggregated lung cancer families, 12q across families and 7p and 4q within a single family. POLR3B, SSPO, DSPP, and PTPN13 are currently the best candidate genes. Impact: Functional work on these genes is planned for future studies and if confirmed would lead to potential biomarkers for risk in cancer.
- Subjects :
- Male
0301 basic medicine
Candidate gene
Lung Neoplasms
Epidemiology
Cell Adhesion Molecules, Neuronal
Sialoglycoproteins
Quantitative Trait Loci
Protein Tyrosine Phosphatase, Non-Receptor Type 13
Biology
Polymorphism, Single Nucleotide
Article
Germline
03 medical and health sciences
0302 clinical medicine
Risk Factors
Exome Sequencing
medicine
Humans
Genetic Predisposition to Disease
Family history
Medical History Taking
Lung cancer
Exome sequencing
Genetics
Extracellular Matrix Proteins
Chromosomes, Human, Pair 12
Haplotype
RNA Polymerase III
Cancer
Phosphoproteins
medicine.disease
Pedigree
030104 developmental biology
Haplotypes
Oncology
030220 oncology & carcinogenesis
Expression quantitative trait loci
Female
Chromosomes, Human, Pair 4
Lod Score
Chromosomes, Human, Pair 7
Subjects
Details
- ISSN :
- 15387755 and 10559965
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Cancer Epidemiology, Biomarkers & Prevention
- Accession number :
- edsair.doi.dedup.....be3f000f89bc1e49a31d731881dce2b8