Abstract
The proto-oncogene PIK3CA has been well studied for its activating mutations and genomic amplifications but not single nucleotide polymorphism (SNP) in thyroid cancer. We investigated SNP rs17849071 (minor allele G and major allele T) in PIK3CA in thyroid tumors in 503 subjects by PCR and sequencing of a region of intron 9 carrying this SNP. This SNP was found in both normal and thyroid tumor tissues as well as in different generations of a studied family, confirming it to be a germline genetic event in thyroid tumor patients. In comparison with normal subjects, a dramatically lower prevalence of the heterozygous genotype G/T at rs17849071 was found in patients with follicular thyroid cancer (FTC). Specifically, rs17849071G/T was found in 15% (18/117) normal subjects vs. 1.3% (1/77) FTC patients, with an odds ratio of 0.07 (95% CI 0.01–0.55; P = 0.001). This represents a 93% risk reduction for FTC with this SNP. In contrast, no difference was seen with benign thyroid neoplasms in which the prevalence of rs17849071G/T was 13.1% (17/130), with an odds ratio of 0.83 (95% CI 0.40–1.69; P = 0.72). There was a trend of lower prevalences of rs17849071G/T and odds ratio in other types of thyroid cancer without statistical significance. We also found an interesting inverse relationship of rs17849071G/T with PIK3CA amplification. With copy number ≥4 defined as copy gain, 2.9% (1/34) rs17849071G/T vs. 19.0% (67/352) rs17849071T/T cases displayed PIK3CA amplification (P = 0.01). Conversely, 1.5% (1/68) cases with PIK3CA amplification vs. 10.4% (33/318) cases without PIK3CA amplification harbored rs17849071G/T (P = 0.01). This provides an explanation for the reciprocal relationship of rs17849071G/T with FTC, since PIK3CA amplification is an important oncogenic mechanism in thyroid cancer, particularly FTC. Thus, the present study uncovers an interesting phenomenon that rs17849071G/T is protective against FTC possibly through preventing PIK3CA amplifications.
Highlights
Thyroid cancer is the most common endocrine malignancy, with 56,460 new cases and 1,780 related deaths estimated for 2012 and a still rapidly rising incidence in the United States [1]
Thyroid cancer can be histologically classified into papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC), and medullary thyroid cancer (MTC), which account for approximately 80%, 15%, 2%, and 3% of all thyroid malignancies, respectively [2,1]
In a subset of 12 cases with rs17849071G found in the primary thyroid tumors, this single nucleotide polymorphism (SNP) was found in all their matched normal thyroid tissues
Summary
Thyroid cancer is the most common endocrine malignancy, with 56,460 new cases and 1,780 related deaths estimated for 2012 and a still rapidly rising incidence in the United States [1]. Thyroid cancer can be histologically classified into papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC), and medullary thyroid cancer (MTC), which account for approximately 80%, 15%, 2%, and 3% of all thyroid malignancies, respectively [2,1]. PTC, FTC and ATC derive from follicular epithelial thyroid cells while MTC derives from parafollicular C cells. Derived from follicular epithelial thyroid cells are the far more common benign thyroid neoplasms, including thyroid adenomas and hyperplasia. An uncommon FTC-like, but histologically and genetically distinct thyroid cancer, Hurthle-cell thyroid cancer (HTC), is derived from follicular-epithelial thyroid cells. FTC and PTC are usually differentiated thyroid cancer. ATC is an undifferentiated and aggressive form of thyroid cancer [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
