Discussion
According to relevant research, the particular genetic mutation has been reported only in Asian regions, in contrast to MUTYH-related common gene mutations in Caucasians [5-8]. MUTYH-associated familial intestinal polyposis caused by this gene also is attenuated compared to regular MAP. MAP occurred mainly in the proximal colon, and polyps are mainly tubular adenomas, some tubular villous adenomas, and occasionally hyperplastic polyps [9]. Interestingly, the vast majority of polyps in this patient were located in the left colon, in contrast to MAP, which occurred in the right colon. However, recent literature has shown that patients associated with MYH deficiency resulting in hyperplastic polyps are not uncommon and present in a condition where hyperplastic polyps coexisted with adenomatous polyps[9-10].This is consistent with the pathologic features of polyps in this patient, with proliferative polyps, tubular adenomas, and choriotubular adenomas growing together.
He has a heterozygous mutation in the MUTYH gene, which is a monoallelic mutation. The clinical severity is low, however, caused by this monoallelic heterozygous mutation was not yet reported in any relevant case. Unlike biallelic mutations, which could accelerate the development of adenomas in subsequent years, according to previous literature and ESGE guidelines, patients with uniallelic mutations rarely developed adenomatous polyposis or had only a slightly increased risk of developing CRC[4、11]. As mild as the description in the literature is, his immunohistochemical results predicted that the tumor had a strong invasive and metastatic capacity. This might indicate the need for closer follow-up care. As understanding increases, there also is a growing body of literature showing that even patients with single allelic mutations have a higher risk of cancer than other normal people [12、13、15]. Tumorigenesis by a mechanism of functional heterozygous somatic deletion of the MUTYH allele in tumors due to monoallelic pathogenic MUTYH germline variants. And the carriers of the monoallelic pathogenic germline variant MUTYH have a higher risk of developing tumors, particularly those with frequent events of loss of heterozygosity [13].
According to the family study, just like the patient in our report, the Clinvar database categorizes his gene as causative, and his mother and daughter have the same gene mutation site, and their colorectal cancer risk was more than approximately three-fold[14-15、16]. And depending on the genetic make-up of mother and daughter, it is more like an autosomal dominant inheritance. In addition, family genealogy analyzes can be used to better evaluate the common mutations in Asian populations in order to better assess and intervene in colorectal cancer hazard in monoallelic carriers [15].
It was worth mentioning that he has an another mutation in LHX4, but the genetic report does not explicitly mention the association with colorectal cancer. At present, the expression pattern of LHX gene in colorectal cancer is still unclear. The literature posits that LHX4 upregulates β-catenin levels in colorectal cancer cell lines, and LHX4 associated mutations or deletion disrupted the direct LHX4-β-catenin interaction , as well as significantly reduced the capability of LHX4 to both combine and trans-increase target gene promoters. Importantly, deletion or mutation of LHX4 also abolished its tumor-promoting function, suggesting that its mediated LHX4-catenin interaction was crucial for LHX4’s tumor suppressor functions[17]. It is unknown whether the progression of colon polyps is balanced when the two genetic mutations are present at the same time. In clinical work, we must pay more attention to the results of patients’ genetic examinations to prevent rare reported gene mutations from being overlooked, and carry out individual follow-up protocols to study in detail the clinical manifestations caused by polygenic mutations.
Malignant tumors accounted for up to 90% of adult intussusception, so if adult intussusception is present, the possibility of tumorigenesis cannot be overlooked and endoscopy should be considered for surveillance screening and regular follow-up [18].
In our case report, patients should appropriately lengthen and shorten the endoscopic follow-up time according to the bowel preparation and whether the pathology is prone to cancer, and individualize the endoscopic polypectomy plan so that the patient’s lesions do not develop as much as possible.