104P - Comprehensive analysis of clinical characteristics and germline status among colorectal cancer patients in a tertiary care center in Thailand

Background

Germline testing has been approved for high-risk colorectal cancer (CRC) patients in Thailand under universal coverage. Analyzing the unique clinical characteristics associated with pathogenic germline variants (PVs) compared to noncarriers could enhance screening criteria tailored to the Thai population.

Methods

CRC patients within our institution were referred to the genetic clinic to assess the potential risk of carrying PVs. Next-generation sequencing (NGS) was conducted from 2020 to 2023 to identify their germline status. Clinical data were retrospectively collected to correlate with their germline results. The evaluation was analyzed using descriptive statistics, Cox regression, and Kaplan-Meier analysis.

Results

Among the 313 CRC patients who underwent NGS, 140 CRC patients, with a median age of 47 years and 58.2% being male, were available for clinical data extraction. Of these, 40 (28.5%) were identified as carrying PVs. Among them, 27 were positive for Lynch syndrome (LS) (MLH1, MSH2, MSH6, and PMS2), while 8 harbored moderate to high penetrance genes, including 5 APC, 2 BRCA2, 1 PTEN, and 3 ATM. Family history of first-degree relatives (FDR) with CRC (any age) emerged as a strong predictor in both LS (p<0.001) and non-LS (p=0.025) groups, along with an FDR of early-onset CRC (<50 years) (LS: p=0.018, non-LS: p=0.012). The LS group demonstrated a preference toward right-sided colon lesions (p=0.01). Of the available LS patients, 19/21 (90.5%) showed MMR deficiency in tissue pathology. The incidence of synchronous/metachronous CRC was up to 29.6% in LS group (p=0.003). At a median follow-up time of 60 (7-453) months, those with PVs and multiple primary cancers tended to have a shorter median time from the first CRC to subsequent events, including metachronous CRC, recurrent CRC, or second cancer in different organs, compared to those without PVs (135 vs. 228 months, p=0.11).

Conclusions

Our study emphasizes the importance of germline testing for high-risk CRC patients. However, further large-scale studies are required to investigate strategies aimed at optimizing tailored screening and advancing management approaches, with the ultimate goal of delivering personalized care.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.