Is rectal cancer inherited by males or females?

Hereditary colorectal cancer is rare in my country, especially patients with hereditary non-polyposis colorectal cancer (Lynch syndrome), which has not attracted the attention of general surgeons in China. Many Lynch syndrome patients are treated as sporadic colorectal cancer. In fact, there are great differences between the two in diagnosis and treatment. So, is rectal cancer inherited in males or females? Let's learn about this issue below.

1. Hereditary non-polyposis colorectal cancer

Hereditary non-polyposis colorectal cancer (LS) is the most common syndrome of hereditary colorectal cancer, accounting for 2%-3% of all colorectal cancers. It is mainly caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Mutations in MLH3, PMS1 and EXO1 have also been reported to be associated with LS.

The disease is inherited in an autosomal dominant manner, but due to incomplete penetrance, age of onset, screening and preventive surgery, not all parents of LS-related gene mutation carriers are cancer patients.

The LS family screening criteria in my country are: there are at least 2 cases of histologically confirmed colorectal cancer patients in the family, 2 of which are parents and children or siblings, and meet any one of the following conditions:

(1) At least one patient had primary colorectal cancer (including adenoma);

(2) at least one case of colorectal cancer occurred before the age of 50;

(3) At least one family member suffers from LS-related extraintestinal malignancies (gastric cancer, endometrial cancer, small intestinal cancer, renal pelvis and ureteral cancer, ovarian cancer, and hepatobiliary system cancer).

2. Classic familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is also a colorectal cancer susceptibility syndrome in which patients have hundreds or thousands of polyps in the colorectum.

FAP is an autosomal dominant genetic disease that often has extracolonic manifestations, including gastric and duodenal polyps, bone tumors, dental abnormalities, desmoid tumors, thyroid and brain tumors, congenital hypertrophy of the retinal pigment epithelium, and epidermoid cysts.

Mild familial adenomatous polyposis

Classic FAP occurs in adolescence, while patients with mild familial adenomatous polyposis (AFAP) often develop polyps in adulthood. Although some patients require surgical colectomy, some patients can be controlled by endoscopic treatment.

Furthermore, patients with AFAP have a lower incidence of extracolonic tumors and desmoid tumors.

Both FAP and AFAP are caused by mutations in the APC gene. APC is a tumor suppressor gene that plays a negative regulatory role in the wnt signaling pathway and is associated with cell migration, adhesion, transcriptional activation, and apoptosis. APC gene mutations lead to the production of truncated protein products, which promote the occurrence and development of tumors. Cases of colorectal cancer caused by APC gene mutations account for approximately 0.5% of all colorectal cancer patients; however, this number is decreasing with early screening of high-risk family members and preventive surgical resection.

MUTYH-associated polyposis

MUTYH-associated polyposis (MAP) is an autosomal recessive genetic disease characterized by multiple colorectal polyps. Its clinical manifestations are similar to those of FAP and AFAP, but the average age of onset is close to middle age, around 50 years old.

Treatment is similar to that for FAP and AFAP and can be surgical or endoscopic, depending on the number and burden of polyps.

Population-based studies have found that approximately one-third of carriers of MUTYH gene mutations develop colorectal cancer without colorectal polyps.

5. Familial colorectal cancer type X

Familial colorectal cancer type X means that three relatives in two generations suffer from colorectal cancer, one of whom is diagnosed before the age of 50, but does not carry mismatch repair genes or have tumors caused by mismatch repair mutations.