Associations of Age With Tumor Genomic Characteristics in Relapsed/Refractory Cancers Interrogated With the NCI-MATCH Trial Targeted Gene Panel Assay.

Abstract

Motivated by the rising incidence of cancers at younger ages, this study compares tumor genomic alterations between adolescents and young adults (AYAs; 18-39 years) and non-AYAs (40 years and older) and explores the relationship with continuous age in patients with relapsed/refractory ovarian, breast, and colorectal cancers accrued to the NCI-MATCH trial. Tumor genomic profiles generated by a next-generation sequencing 143-gene panel (NCI-MATCH assay, v2) were analyzed for association with age (AYA/total: 21/455 ovarian, 27/576 breast, 43/759 colorectal cancers). For each gene, AYA and non-AYA DNA alteration proportions were compared (Fisher exact test) and alteration association with continuous age (logistic regression) was evaluated (false discovery rate‑adjusted <i>P</i> value <.1 statistically significant). For colorectal cancer, sex-stratified analysis was also performed. No significant AYA versus non-AYA differences were observed in the prevalence of gene mutations (single nucleotide variant [SNV]/indel). A significant association of gene amplification with AYAs (odds ratio [OR], 95% CI) was <i>CCND1</i> (0.2, 0.1-0.4), favoring AYAs in breast cancer. Examining age as a continuous variable, significant associations of gene mutations (SNV/indel) with older age, expressed as 5-year OR (OR [95% CI]), were observed: <i>TP53</i> (1.3 [1.1 to 1.4]), ovarian cancer; <i>CDH1</i> (1.4 [1.2 to 1.6]) and <i>PIK3CA</i> (1.1 [1.1 to 1.2]), breast cancer; and <i>BRAF</i> (1.4 [1.2 to 1.7]), female colorectal cancer. Associations with younger age included <i>SMAD4</i> (0.8 [0.7 to 0.9]), male colorectal cancer. Significant associations of gene amplification with age (continuous) were as follows: <i>CCNE1</i> (1.3 [1.1 to 1.6]), older ovarian cancer, and <i>CCND1</i> (0.8 [0.8 to 0.9]), younger breast cancer. Comparing AYAs with non-AYAs among patients having relapsed/refractory disease, no significant differences in SNV/indel prevalence were observed, but <i>CCND1</i> amplifications were more prevalent in AYA breast cancer. For several genes, DNA alterations were associated with continuous age and may depend on sex in colorectal cancer.