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Thyroid cancer was expected to have an annual incidence in the United States of 37,340 cases in 2008 and has become the sixth most common cancer in women.1 There has been a 2.4-fold increase in the incidence of thyroid cancer in the United States over the past 30 years, from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2003, with virtually the entire increase attributable to the papillary type, particularly cancers smaller than 2 cm in diameter.2

Papillary thyroid cancer (PTC), which is a differentiated type of thyroid cancer derived from follicular epithelial cells, is the most common histologic type of thyroid cancer, occurring in about 80% of cases.3 Multiple subtypes of PTC have been described and include the classical form that contains areas of a predominantly papillary growth pattern as well as follicles; a follicular variant of PTC (FVPTC) that grows in a follicular pattern; and more aggressive variants, including the tall cell, columnar cell, diffuse sclerosing, and insular variants of PTC.4

Both genetic and environmental factors may increase the risk of developing PTC. About 3% of cases of PTC are familial.5 Some familial syndromes known to be associated with PTC include familial adenomatous polyposis (FAP) and its variant, Gardner syndrome (both caused by a mutation in the APC gene); Cowden syndrome (also known as multiple hamartoma syndrome; caused by a mutation in the PTEN gene); and Carney complex (caused by a mutation in the PRKAR1A gene).6,7 A family history of PTC in two first-degree relatives increases the risk of PTC three- to nine-fold, and these families are likely part of a familial nonmedullary thyroid cancer (FNMTC) kindred, whose specific genetic defect has not yet been determined.8

The strongest evidence linking thyroid cancer to an environmental cause exists for exposure to ionizing radiation.9 These data are derived from studies of children who were exposed to the nuclear fallout from Chernobyl, adult survivors of the atomic bombings of Hiroshima and Nagasaki, and patients who received head and neck radiotherapy in childhood for the treatment of a variety of benign conditions such as enlarged tonsils, tinea capitis, acne, or an enlarged thymus.

Other factors that have been investigated to determine their impact on the risk of developing thyroid cancer include hormonal factors, iodine intake, and the presence of Hashimoto's thyroiditis. Even though the majority of patients with PTC are women, no convincing hormonal associations have been elucidated.10 Studies examining the influence of iodine intake on the risk of thyroid cancer have shown conflicting results, and at the present time, iodine intake is generally not considered to affect a patient's risk of developing thyroid cancer.11 The influence of Hashimoto's thyroiditis on thyroid cancer risk is controversial, but large studies have shown an increased prevalence of Hashimoto's thyroiditis in patients with PTC.12,13

PTC is more common in women ...

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