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.