An exploratory analysis of the genetic alteration associated with early-onset gastric and colorectal cancer using a large-scale nationwide database of Japan (C-CAT).
Authors: Izuma Nakayama, Naoki Miyazaki, Risa Ueno, Ippei Fukada, Kensei Yamaguchi, Eiji Shinozaki
Journal: Journal of Clinical Oncology (2024)

4058 Background: The recent global concern about the early onset cancer (EOC) has been rising in the field of GI cancers. Precision oncology based on comprehensive genome profile (CGP) test is anticipated to attribute the improvement of cancer treatment for EOC. This study explored the genetic alteration of EOC and association with genome matched therapy in colorectal cancer (CRC) and gastric or gastroesophageal junction cancer (G/GEJC). Methods: We retrospectively assessed Japanese nationwide, the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. Pts meets following eligibility criteria were enrolled. 1) Pts received the reimbursed CGP tests between June 2019 and May 2023 in Japan, 2) pts registered as CRC or G/GEJC, 3) pts agreed with the utilization of their data. We defined EOC as diagnosed at less than 50 and 40 in EO-CRC and EO-G/GEJC, respectively. We investigated the genomic alterations of EOC and compared the genes with a difference in frequency of 5% or more between earlier and later onset cancer of disease. The transition rate to the subsequent matched therapy was compared between EOC and non-EOC. This study was approved by both the ethics committee of Cancer Institute Hospital of JFCR (No. 2022-GB-121) and C-CAT data utilization review board (No. AP20230309-01N). Results: Among a total of 8,180 eligible pts, 1,289 (19.9%) and 123 (7.2%) EOC were identified in CRC and G/GEJC, respectively. Tissue based assay with Foundation One (n = 6.591, 80.6%) was most frequently employed as CGP test. TP53 (84.1%), APC (77.2%) and KRAS (49.5%) mutation were most frequently occurred in EO CRC. Meanwhile, TP53 (64.2%), CDH1 (36.5%) and ARID1A (17.1%) mutation were the most prevalent in EO G/GEJC. Among the top 30th somatically mutated genes in EO CRC and EO G/GEJC, 31 (96.9%) and 29 (85.3%) genes shared with non-EO in CRC and G/GEJC, respectively. Notably, the proportion of shared genes was significantly decline to 21 (71.9%) and 18 (52.9%) in CRC and G/GEJC when they compared between pts aged &lt;30 and ≥30 years old. The proportion of pts harboring at least one actionable mutation was 42.3% in EO CRC similar to that of non-EO CRC (43.2%) and 19.5% in EO G/GEJC and lower than that of non-EO G/GEJC (32.2%), respectively. The proportions of individuals who received targeted therapy as recommended by CGP test were all approximately 5% (EOC vs. non-EOC: 6.4% vs. 5.6% in CRC and 4.1% vs. 4.4% in G/GEJC). The treatment access rate was not improved in very young pts (aged &lt;30). Conclusions: Genomic alterations were mostly shared between EOC and non-EOC in pts with CRC and G/GEJC. The mutation profile apparently differs between earlier onset (&lt;30) and later onset (≥30) both in CRC and G/GEJC. Very limited proportion of EOC could access the matched therapy after CGP test in the treatment of CRC and G/GEJC as well as non-EOC.