Cargando…

Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset

IMPORTANCE: The incidence of appendiceal cancer (AC) is rising, particularly among individuals younger than 50 years (early-onset AC), with unexplained etiologies. The unique spectrum of somatic cancer gene variations among patients with early-onset AC is largely undetermined. OBJECTIVE: To characte...

Descripción completa

Detalles Bibliográficos
Autores principales: Holowatyj, Andreana N., Eng, Cathy, Wen, Wanqing, Idrees, Kamran, Guo, Xingyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726634/
https://www.ncbi.nlm.nih.gov/pubmed/33295976
http://dx.doi.org/10.1001/jamanetworkopen.2020.28644
_version_ 1783620922790379520
author Holowatyj, Andreana N.
Eng, Cathy
Wen, Wanqing
Idrees, Kamran
Guo, Xingyi
author_facet Holowatyj, Andreana N.
Eng, Cathy
Wen, Wanqing
Idrees, Kamran
Guo, Xingyi
author_sort Holowatyj, Andreana N.
collection PubMed
description IMPORTANCE: The incidence of appendiceal cancer (AC) is rising, particularly among individuals younger than 50 years (early-onset AC), with unexplained etiologies. The unique spectrum of somatic cancer gene variations among patients with early-onset AC is largely undetermined. OBJECTIVE: To characterize the frequency of somatic variations and genomic patterns among patients with early-onset (age <50 years) vs late-onset (age ≥50 years) AC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included individuals aged 18 years and older diagnosed with pathologically verified AC. Cases with clinical-grade targeted sequencing data from January 1, 2011, to December 31, 2019, were identified from the international clinicogenomic data-sharing consortium American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE). Data analysis was conducted from May to September 2020. EXPOSURES: Age at disease onset. MAIN OUTCOMES AND MEASURES: Somatic variation prevalence and spectrum in AC patients was determined. Variation comparisons between early-onset and late-onset AC were evaluated using multivariable logistic regression with adjustment for sex, race/ethnicity, histological subtype, sequencing center, and sample type. RESULTS: In total 385 individuals (mean [SD] age at diagnosis, 56.0 [12.4] years; 187 [48.6%] men; 306 [79.5%] non-Hispanic White individuals) with AC were included in this study, and 109 patients (28.3%) were diagnosed with early-onset AC. Race/ethnicity differed by age at disease onset; non-Hispanic Black individuals accounted for a larger proportion of early-onset vs late-onset cases (9 of 109 [8.3%] vs 11 of 276 [4.0%]; P = 0.04). Compared with patients aged 50 years or older at diagnosis, patients with early-onset AC had significantly higher odds of presenting with nonsilent variations in PIK3CA, SMAD3, and TSC2 (PIK3CA: odds ratio [OR], 4.58; 95% CI, 1.72-12.21; P = .002; SMAD3: OR, 7.37; 95% CI, 1.24-43.87; P = .03; TSC2: OR, 12.43; 95% CI, 1.03-149.59; P = .047). In contrast, patients with early-onset AC had a 60% decreased odds of presenting with GNAS nonsilent variations compared with patients with late-onset AC (OR, 0.40; 95% CI, 0.21-0.76, P = .006). By histological subtype, young patients with mucinous adenocarcinomas of the appendix had 65% decreased odds of variations in GNAS compared with late-onset cases in adjusted models (OR, 0.35; 95% CI, 0.15-0.79; P = .01). Similarly, patients with early-onset nonmucinous appendiceal adenocarcinomas had 72% decreased odds of presenting with GNAS variations vs late-onset cases, although these findings did not reach significance (OR, 0.28; 95% CI, 0.07-1.14; P = .08). GNAS and TP53 variations were mutually exclusive in ACs among early-onset and late-onset cases (P < .05). CONCLUSIONS AND RELEVANCE: In the study, AC diagnosed among younger individuals harbored a distinct genomic landscape compared with AC diagnosed among older individuals. Development of therapeutic modalities that target these unique molecular features may yield clinical implications specifically for younger patients.
format Online
Article
Text
id pubmed-7726634
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher American Medical Association
record_format MEDLINE/PubMed
spelling pubmed-77266342020-12-17 Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset Holowatyj, Andreana N. Eng, Cathy Wen, Wanqing Idrees, Kamran Guo, Xingyi JAMA Netw Open Original Investigation IMPORTANCE: The incidence of appendiceal cancer (AC) is rising, particularly among individuals younger than 50 years (early-onset AC), with unexplained etiologies. The unique spectrum of somatic cancer gene variations among patients with early-onset AC is largely undetermined. OBJECTIVE: To characterize the frequency of somatic variations and genomic patterns among patients with early-onset (age <50 years) vs late-onset (age ≥50 years) AC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included individuals aged 18 years and older diagnosed with pathologically verified AC. Cases with clinical-grade targeted sequencing data from January 1, 2011, to December 31, 2019, were identified from the international clinicogenomic data-sharing consortium American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE). Data analysis was conducted from May to September 2020. EXPOSURES: Age at disease onset. MAIN OUTCOMES AND MEASURES: Somatic variation prevalence and spectrum in AC patients was determined. Variation comparisons between early-onset and late-onset AC were evaluated using multivariable logistic regression with adjustment for sex, race/ethnicity, histological subtype, sequencing center, and sample type. RESULTS: In total 385 individuals (mean [SD] age at diagnosis, 56.0 [12.4] years; 187 [48.6%] men; 306 [79.5%] non-Hispanic White individuals) with AC were included in this study, and 109 patients (28.3%) were diagnosed with early-onset AC. Race/ethnicity differed by age at disease onset; non-Hispanic Black individuals accounted for a larger proportion of early-onset vs late-onset cases (9 of 109 [8.3%] vs 11 of 276 [4.0%]; P = 0.04). Compared with patients aged 50 years or older at diagnosis, patients with early-onset AC had significantly higher odds of presenting with nonsilent variations in PIK3CA, SMAD3, and TSC2 (PIK3CA: odds ratio [OR], 4.58; 95% CI, 1.72-12.21; P = .002; SMAD3: OR, 7.37; 95% CI, 1.24-43.87; P = .03; TSC2: OR, 12.43; 95% CI, 1.03-149.59; P = .047). In contrast, patients with early-onset AC had a 60% decreased odds of presenting with GNAS nonsilent variations compared with patients with late-onset AC (OR, 0.40; 95% CI, 0.21-0.76, P = .006). By histological subtype, young patients with mucinous adenocarcinomas of the appendix had 65% decreased odds of variations in GNAS compared with late-onset cases in adjusted models (OR, 0.35; 95% CI, 0.15-0.79; P = .01). Similarly, patients with early-onset nonmucinous appendiceal adenocarcinomas had 72% decreased odds of presenting with GNAS variations vs late-onset cases, although these findings did not reach significance (OR, 0.28; 95% CI, 0.07-1.14; P = .08). GNAS and TP53 variations were mutually exclusive in ACs among early-onset and late-onset cases (P < .05). CONCLUSIONS AND RELEVANCE: In the study, AC diagnosed among younger individuals harbored a distinct genomic landscape compared with AC diagnosed among older individuals. Development of therapeutic modalities that target these unique molecular features may yield clinical implications specifically for younger patients. American Medical Association 2020-12-09 /pmc/articles/PMC7726634/ /pubmed/33295976 http://dx.doi.org/10.1001/jamanetworkopen.2020.28644 Text en Copyright 2020 Holowatyj AN et al. JAMA Network Open. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Holowatyj, Andreana N.
Eng, Cathy
Wen, Wanqing
Idrees, Kamran
Guo, Xingyi
Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset
title Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset
title_full Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset
title_fullStr Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset
title_full_unstemmed Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset
title_short Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset
title_sort spectrum of somatic cancer gene variations among adults with appendiceal cancer by age at disease onset
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726634/
https://www.ncbi.nlm.nih.gov/pubmed/33295976
http://dx.doi.org/10.1001/jamanetworkopen.2020.28644
work_keys_str_mv AT holowatyjandreanan spectrumofsomaticcancergenevariationsamongadultswithappendicealcancerbyageatdiseaseonset
AT engcathy spectrumofsomaticcancergenevariationsamongadultswithappendicealcancerbyageatdiseaseonset
AT wenwanqing spectrumofsomaticcancergenevariationsamongadultswithappendicealcancerbyageatdiseaseonset
AT idreeskamran spectrumofsomaticcancergenevariationsamongadultswithappendicealcancerbyageatdiseaseonset
AT guoxingyi spectrumofsomaticcancergenevariationsamongadultswithappendicealcancerbyageatdiseaseonset