High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

Background In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients <50 years old compared to western populations, possibly due to a higher frequency of Lynch Syndrome (LS) in CRC patients. We aim to examine the association of KRAS and PIK3CA mutation with LS. Methods In this cross-sectional study, the PCR-HRM-based test was used for screening of MSI mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF(V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples. Results All the samples (n=244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples respectively. PIK3CA mutation was significantly associated with female sex and lower levels of TILs in 62/107 (57.94%) and 26/107 (30.23%) samples respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients. Conclusions High probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.