The impact of family history on non-medullary thyroid cancer

Abstract

Introduction Around 10% of patients with non-medullary thyroid cancer (NMTC) will have a positive family history for the disease. Although many will be sporadic, families where 3 first-degree relatives are affected can be considered to represent true familial non-medullary thyroid cancer (FNMTC). The genetic basis, impact on clinical and pathological features, and overall effect on prognosis are poorly understood. Methods A literature review identified articles which report on genetic, clinical, therapeutic and screening aspects of FNMTC. The results are presented to allow an understanding of the genetic basis and the impact on clincal-pathological features and prognosis in order to inform clinical decision making. Results The genetic basis of FNMTC is unknown. Despite this, significant progress has been made in identifying potential susceptibility genes. The lack of a test for FNMTC has led to a clinical definition requiring a minimum of 3 first-degree relatives to be diagnosed with NMTC. Although some have shown an association with multi-centric disease, younger age and increased rates of extra-thyroidal extension and nodal metastases, these findings are not supported by all. The impact of FNMTC is unclear with all groups reporting good outcome, and some finding an association with more aggressive disease. The role of screening remains controversial. Conclusion FNMTC is rare but can be diagnosed clinically. Its impact on prognostic factors and the subsequent role in influencing management is debated. For those patients who present with otherwise low-risk differentiated thyroid cancer, FNMTC should be included in risk assessment when discussing therapeutic options.

Bethesda thyroid categories and family history of thyroid disease

“…According to the available literature, the familial thyroid cancer is rare but recognized condition . It is known that it may present in younger age and with more aggressive disease than usual, with higher rate of lymph node metastasis.…”

“…The link between the family history and the risk of developing thyroid cancer was investigated in several large and many smaller studies. In a review of Nixon and colleagues, it was noted that familial nonmedullary thyroid cancer is rare but can be diagnosed clinically, while its impact on prognostic factors and the subsequent role in influencing management is not yet clearly defined . In another retrospective hospital‐based case‐control study which included 288 patients with sporadic DTC and 591 cancer‐free controls, family history of thyroid cancer in first‐degree relatives was associated with increased risk of developing DTC (adjusted odds ratio 4.1; 95% confidence interval 1.7‐9.9).…”

Growing incidence of thyroid carcinoma in recent years: Factors underlying overdiagnosis

“…For the case of well-differentiated thyroid cancer, although genetic and familial associations have been shown, these are rare and difficult to differentiate from the effect of the more intense scrutiny of family members after diagnosis of the index case. 68 Finally, anxiety due to the "fear" of cancer can trigger both an initial referral and more intense investigation. Because many of the patients in whom incidental detection occurs are middle-aged women, the fear of dying in young mothers can lead to pressure for physicians to arrange imaging tests to look for the "occult" cancer.…”

“…Due to the occult disease prevalence, the possibility of finding a nodule by ultrasound is close to 70%, and approximately 5%‐30% of these asymptomatic nodules are ultimately confirmed as a thyroid carcinoma. For the case of well‐differentiated thyroid cancer, although genetic and familial associations have been shown, these are rare and difficult to differentiate from the effect of the more intense scrutiny of family members after diagnosis of the index case . Finally, anxiety due to the “fear” of cancer can trigger both an initial referral and more intense investigation.…”

The clinicopathologic characteristics of familial and sporadic papillary thyroid carcinoma in Turkish patients

“…How the number of affected members is associated with tumour aggressiveness remains unknown. Some studies showed that fPTC with 3 or more affected members have more aggressive features than with 2 affected members [9,11,16,17,27]. However, there is also contradictory data [14,15,23].…”