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Supplementary Tables 1-7 and Figures 1-5 from Germline Genetic Variants and Lung Cancer Survival in African Americans

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posted on 2023-03-31, 14:04 authored by Carissa C. Jones, William S. Bush, Dana C. Crawford, Angela S. Wenzlaff, Ann G. Schwartz, John K. Wiencke, Margaret R. Wrensch, William J. Blot, Stephen J. Chanock, Eric L. Grogan, Melinda C. Aldrich

SUPPLEMENTAL TABLE 1. Summary of the five previously reported lung cancer survival GWAS variants examined in the present study. SUPPLEMENTAL TABLE 2. Descriptive characteristics of African Americans with NSCLC participating in the KCI/WSU and UCSF studies. SUPPLEMENTAL TABLE 3. Allele frequency for the five variants previously associated with lung cancer survival in the NHGRIEBI GWAS Catalog in the SCCS (N=275), KCI/WSU (N=312), and UCSF (N=284) populations. Allele frequencies are also presented for the ASW 1000 Genomes African American reference population and for the 1000 Genomes reference population that matches the racial/ethnic group of the original discovery population (CEU or CHB). SUPPLEMENTAL TABLE 4. Adjusted multivariable Cox proportional hazards model results for African Americans with incident non-small cell lung cancer participating in the Southern Community Cohort Study (N=264) for the five candidate SNPs previously associated with lung cancer survival from the NHGRI GWAS catalog. SUPPLEMENTAL TABLE 5. Stage-stratified multivariable Cox proportional hazards results for the association of rs1878022 and overall survival in the SCCS and pooled KCI/WSU and UCSF populations. SUPPLEMENTAL TABLE 6. Allele frequency for common variants associated survival in the SCCS (N=275), KCI/WSU (N=312), and UCSF (N=284) populations. Allele frequencies are also presented for the ASW 1000 Genomes African American reference population. SUPPLEMENTAL TABLE 7. Adjusted multivariable Cox proportional hazards results for African Americans with incident non-small cell lung cancer participating in the Southern Community Cohort Study (N=264) for common variants assayed by the Illumina HumanExome BeadChip v1.1. SUPPLEMENTAL FIGURE 1. Flow chart of quality control (QC) for the SCCS genotyping data. SUPPLEMENTAL FIGURE 2. Distribution of stage at diagnosis across the SCCS (N=286), KCI/WSU (N=316), and UCSF (N=298.) SUPPLEMENTAL FIGURE 3. Global genetic ancestry estimates for African Americans with NSCLC participating in the (A) SCCS, (B) KCI/WSU, and (C) UCSF study populations.SUPPLEMENTAL FIGURE 4. Linkage disequilibrium (LD) patterns +/-10kb surrounding the CMKLR1 gene region in the YRI and CEU populations (A and B, respectively) from 1000 Genomes (phase 3). LD patterns surrounding rs1878022 (denoted by black arrow) are presented as inserts. 1000 Genomes data and Haploview software were utilized to display r2 values (filters:Hardy-Weinberg p-value > 0.001, genotyping efficiency > 90%, and minor allele frequency >0.05).SUPPLEMENTAL FIGURE 5. H3K4me1 and H3K27Ac histone modification marks surrounding rs1878022 in the CMKLR1 gene, visualized using the UCSC Genome Browser. Marks in (A) are specific to normal human lung fibroblast (NHLF) cell lines from the ENCODE project. Marks in (B) are for all cell lines (GM12878, H1-hESC, HSMM, HUVEC, K562, NHEK, and NHLF) in the ENCODE project.

Funding

Department of Defense Early Investigator Synergistic Idea Award

NIH/National Cancer Institute

Training Program on Genetic Variation and Human Phenotypes

National Institute of General Medical Sciences

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NIH/NIGMS

Veterans Affairs Career Development Award

NIH

Department of Health and Human Services

Centers for Disease Control and Prevention (CDC)

History

ARTICLE ABSTRACT

Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases.Methods: Incident non–small cell lung cancer cases (N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies (N = 316 and 298) were used for replication.Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54–0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71–0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33–0.66).Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene–environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival.Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288–95. ©2017 AACR.