Polymorphisms in bone morphogenetic protein 3 and the risk of papillary thyroid cancer

Abstract

Abstract. Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGFβ) superfamily with well-described functions in bone formation. Although disrupted BMP signaling in tumor development has been investigated, a genetic association for BMP3 in papillary thyroid cancer (PTC) has remained largely unexplored. In this study, we investigated whether BMP3 single nucleotide polymorphisms (SNPs) are associated with the development of PTC and its clinicopathological features. A total of 103 PTC patients and 324 control subjects were enrolled. One promoter SNP (rs13138132; -1919C/A) and one missense mutation (rs3733549; Arg192Gln) in BMP3 were genotyped by direct sequencing. SNPStats, SNPAnalyzer, Helixtree and Haploview version 4.2 were used to evaluate the genetic data. Multiple logistic regression models were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and P-values. The missense SNP (rs3733549) was weakly associated with the development of PTC in a codominant model (AA vs. GG; P=0.017) and a recessive model (AA vs. GG/GA; P=0.023). Additionally, in an analysis according to clinicopathological features, rs13138132 was significantly associated with extrathyroidal invasion in a codominant model (CA vs. CC; P=0.006) and a dominant model (CA/AA vs. CC; P=0.0023). We also identified that the frequency of the A allele in the promoter SNP (rs13138132) was increased in PTC patients with extrathyroidal invasion (P=0.004). Our data suggest that rs3733549 in BMP3 is associated with the development of PTC and that the A allele of rs13138932 in BMP3 is a risk factor for extrathyroidal invasion. IntroductionThyroid cancer is the most common type of endocrine malignancy, accounting for approximately 1% of all cases of cancer. It is the most rapidly increasing cancer among females and the second most rapidly increasing cancer among males. Histologically, thyroid cancer is classified as papillary thyroid cancer (PTC), follicular thyroid cancer, medullary thyroid cancer or undifferentiated or anaplastic thyroid cancer. Of these, PTC is the most common type, and it accounts for 85-90% of all thyroid malignancies (1,2). Although the etiology of PTC is unclear, environmental factors, including radiation, diet, smoking and hormones, have been identified to affect the pathogenesis of thyroid cancer (3,4). Genetic predisposition has also been implicated as a risk factor for thyroid cancer development (5,6).Bone morphogenic proteins (BMPs) have been demonstrated to play an important role during development (particularly during bone formation) and in the regulation of various cellular processes, including cell proliferation, apoptosis and differentiation (7). Evidence suggests that BMPs are important in tumorigenesis (8-10). BMPs are members of the transforming growth factor beta (TGFβ) family; thus, BMPs utilize a similar signaling cascade to that of TGFβ. BMPs have been identified to utilize the SMAD signaling pathway for their growth suppressive effects, and also to affect PTEN and p21 (W...

Pattern of Thyroid Cancer and Its Associated Factors Among Thyroid Patients Underwent Thyroidectomy at Jimma Medical Center, Southwest Ethiopia; A Four Years Retrospective Review

“…Accordingly, about six variables (duration of the disease, marital status, family history of the disease, nodularity, surface and border of the thyroid mass) were the candidate variables in binary logistic regression (p-value < 0.25) and nally, three variables (duration of the disease (> 10 years), surface (rough) and border (irregular) of the thyroid mass) were identi ed as the predictors of thyroid malignancy with AOR 0.05(0.004-0.60, P-v = 0.016; 1.9(1.17-5.8), P-v = 0.012 and 2.5(1.13-16.16), P-v < 0.001 respectively as detailed in Table 4. [27][28][29].…”

“…PTC is the most common type and it accounts for 85-90% of all thyroid cancer cases [27][28][29][30] followed by FTC which is the second common carcinoma constituting about 5-10% of all thyroid cancers [31][32][33]. Medullary thyroid tumors accounts about 5-10% of all thyroid carcinoma and are familial in approximately 25% of cases [34].…”

BMP3 Affects Cortical and Trabecular Long Bone Development in Mice

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