Which thyroid cancers are hereditary?

Some people with thyroid cancer carry some abnormal genes, but most do not inherit them. In other words, if you have thyroid cancer, it does not mean that your relatives will also have the disease.

So, is there any thyroid cancer that is inherited?

Yes.

There are two types of thyroid cancer that may be inherited.

familial non-medullary thyroid carcinoma (FNMTC)

Hereditary medullary thyroid cancer (HMTC)

They are both “autosomal dominant” diseases, what does that mean? It means that if one parent has the disease, there is a 50% chance that the child will inherit the “bad gene” and develop the disease.

Familial non-myeloid thyroid cancer (FNMTC)

The majority of FNMTCs are papillary, with the remainder follicular, accounting for about 5% of differentiated thyroid cancers. FNMTC has some unique features compared to “disseminated” non-medullary carcinomas, such as multiple foci, more aggressiveness, tendency to metastasize early, and high recurrence rates.

FNMTC can be divided into two categories:

Occurring alone

While FNMTC is a genetic disease, the presence of 2 cases in a family line does not necessarily indicate heritability and may be associated with shared exposure to risk factors (e.g., same diet, lifestyle, etc.). Some studies suggest that if there are only 2 cases of non-myeloid cancer in a first-degree family relative (children, close siblings), the probability that this family is hereditary is only 31% to 38%; if there are 3 or more patients, the probability is greater than 94%.

The exact pathogenesis of FNMTC is unknown, and it may be characterized by mutations in specific genes, so testing for genes such as BRAF, the RET gene, and the TERT promoter gene can be one of the markers for disease diagnosis and for determining patient outcome. However, it is not these genes that directly cause FNMTC.

As a manifestation of familial tumor syndrome.

Familial adenomatous polyposis (FAP). Patients have tens, hundreds, or even thousands of polyps in the intestine and may have multiple adenomas in the colorectum. It is often accompanied by thyroid cancer.

Gardner syndrome (GCS). Also called familial colonic polyposis, this is a form of FAP. Patients may first develop soft tissue tumors such as leiomyosarcomas, facetomas, and lipomas, and then grow multiple colon polyps. It can be associated with papillary thyroid cancer.

Cowden disease, papules and nodules on the face, oral mucosa, and arms. Patients have a higher than normal risk of both benign thyroid lesions and thyroid cancer.

Carney complex (CNC). This is a rare cutaneous mucinous tumor that can be associated with thyroid cancer.

If you or a family member has any of these conditions, it is important to consult with your doctor to be on the lookout for thyroid cancer.

Hereditary medullary thyroid carcinoma (HMTC)

Hereditary medullary thyroid carcinoma (MTC) is hereditary in about 15% to 25% of cases and is divided into 3 subtypes:

multiple endocrine neoplasia type IIa (MEN2A)

multiple endocrine neoplasia type IIb (MEN2B)
familial endocrine neoplasia type IIb (MEN2B)
Familial medullary thyroid cancer (FMTC).

Most patients with HMTC have RET proto-oncogene mutations, with up to 98% in MEN2A, 95% in MEN2B, and 85% in FMTC. Once the RET gene mutation is carried, the majority of cases develop, even in childhood.

Mutation sites (codons) in the RET gene vary, making HMTC different in terms of age at onset and life expectancy. The American Thyroid Association (ATA) has sorted this out and recommends that first-degree relatives (children, biological siblings) and second-degree relatives [nieces and nephews] of HMTC patients be screened for mutations in the RET gene and, if they carry the mutation, require standardized thyroid cancer screening and prophylactic resection (Table 1 ).

Risk level

Table 1: Treatment recommendations for RET gene mutation carriers
RET gene mutation codon	Recommended Screening Time	Recommended time for preventive surgery
Highest risk	918		Months to 1 year
High risk	634, 883	From age 3	From age 5
Medium Risk	533, 609, 611, 618, 620, 630, 666, 768, 790, 804, 891, 912	from age 5	Childhood or young adulthood

In this country, doctors usually recommend that all children of patients with medullary carcinoma be screened by having blood drawn to check levels of tumor markers [(carcinoembryonic antigen, CEA) and serum calcitonin (CT)]. If these two indicators are found to be abnormal, doctors will usually recommend genetic testing. However, this test is not yet widely available, and you should consult your doctor for specific questions.