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

Kim,Young  Ock; Hong,Il  Ki; Eun,Young  Gyu; Nah,Seong‑Su; Lee,Soojeong; Heo,Su‑Hak; Kim,Hyung-Kee; Song,Ho‑Yeon; Kim,Hak‑Jae

doi:10.3892/ol.2012.962

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

Authors:
- Young Ock Kim
- Il Ki Hong
- Young Gyu Eun
- Seong‑Su Nah
- Soojeong Lee
- Su‑Hak Heo
- Hyung-Kee Kim
- Ho‑Yeon Song
- Hak‑Jae Kim
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Affiliations: Development of Ginseng and Medical Plants Research Institute, Rural Administration, Eumseong, Republic of Korea, Department of Otolaryngology‑Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, Republic of Korea, Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea, Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea , Soonchunhyang Medical Research Institute, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea , Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea
Published online on: October 10, 2012 https://doi.org/10.3892/ol.2012.962
Pages: 336-340

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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.

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1	Hundahl SA, Fleming ID, Fremgen AM and Menck HR: A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 [see comments]. Cancer. 83:2638–2648. 1998.PubMed/NCBI
2	Dohan O, Baloch Z, Banrevi Z, Livolsi V and Carrasco N: Rapid communication: predominant intracellular overexpression of the Na(+)/I(−) symporter (NIS) in a large sampling of thyroid cancer cases. J Clin Endocrinol Metab. 86:2697–2700. 2001.PubMed/NCBI
3	Kondo T, Ezzat S and Asa SL: Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 6:292–306. 2006. View Article : Google Scholar : PubMed/NCBI
4	Grubbs EG, Rich TA, Li G, Sturgis EM, Younes MN, et al: Recent advances in thyroid cancer. Curr Probl Surg. 45:156–250. 2008. View Article : Google Scholar
5	Malchoff CD and Malchoff DM: Familial nonmedullary thyroid carcinoma. Cancer Control. 13:106–110. 2006.PubMed/NCBI
6	Sturgis EM and Li G: Molecular epidemiology of papillary thyroid cancer: in search of common genetic associations. Thyroid. 19:1031–1034. 2009. View Article : Google Scholar : PubMed/NCBI
7	Ducy P and Karsenty G: The family of bone morphogenetic proteins. Kidney Int. 57:2207–2214. 2000. View Article : Google Scholar : PubMed/NCBI
8	Nosho K, Yamamoto H, Adachi Y, Endo T, Hinoda Y, et al: Gene expression profiling of colorectal adenomas and early invasive carcinomas by cDNA array analysis. Br J Cancer. 92:1193–1200. 2005. View Article : Google Scholar : PubMed/NCBI
9	Koehler A, Bataille F, Schmid C, Ruemmele P, Waldeck A, et al: Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage. J Pathol. 204:65–74. 2004. View Article : Google Scholar : PubMed/NCBI
10	Kraunz KS, Nelson HH, Liu M, Wiencke JK and Kelsey KT: Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer. Br J Cancer. 93:949–952. 2005. View Article : Google Scholar : PubMed/NCBI
11	Beck SE and Carethers JM: BMP suppresses PTEN expression via RAS/ERK signaling. Cancer Biol Ther. 6:1313–1317. 2007.PubMed/NCBI
12	Beck SE, Jung BH, Del Rosario E, Gomez J and Carethers JM: BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Cell Signal. 19:1465–1472. 2007. View Article : Google Scholar : PubMed/NCBI
13	Tomlinson IP, Carvajal-Carmona LG, Dobbins SE, Tenesa A, Jones AM, et al: Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS Genet. 7:e10021052011. View Article : Google Scholar : PubMed/NCBI
14	Fernandez-Rozadilla C, de Castro L, Clofent J, Brea-Fernandez A, Bessa X, et al: Single nucleotide polymorphisms in the Wnt and BMP pathways and colorectal cancer risk in a Spanish cohort. PLoS One. 5:e126732010. View Article : Google Scholar : PubMed/NCBI
15	Park SW, Hur SY, Yoo NJ and Lee SH: Somatic frameshift mutations of bone morphogenic protein receptor 2 gene in gastric and colorectal cancers with microsatellite instability. APMIS. 118:824–829. 2010. View Article : Google Scholar : PubMed/NCBI
16	Amedee J, Bareille R, Rouais F, Cunningham N, Reddi H, et al: Osteogenin (bone morphogenic protein 3) inhibits proliferation and stimulates differentiation of osteoprogenitors in human bone marrow. Differentiation. 58:157–164. 1994. View Article : Google Scholar : PubMed/NCBI
17	Loh K, Chia JA, Greco S, Cozzi SJ, Buttenshaw RL, et al: Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development. Genes Chromosomes Cancer. 47:449–460. 2008. View Article : Google Scholar : PubMed/NCBI
18	Chen XR, Wang JW, Li X, Zhang H and Ye ZY: Role of BMP3 in progression of gastric carcinoma in Chinese people. World J Gastroenterol. 16:1409–1413. 2010. View Article : Google Scholar : PubMed/NCBI
19	Kisiel JB, Yab TC, Taylor WR, Chari ST, Petersen GM, et al: Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates. Cancer. 118:2623–2631. 2012. View Article : Google Scholar : PubMed/NCBI
20	Dai Z, Popkie AP, Zhu WG, Timmers CD, Raval A, et al: Bone morphogenetic protein 3B silencing in non-small-cell lung cancer. Oncogene. 23:3521–3529. 2004. View Article : Google Scholar : PubMed/NCBI
21	Ronneberg JA, Fleischer T, Solvang HK, Nordgard SH, Edvardsen H, et al: Methylation profiling with a panel of cancer related genes: association with estrogen receptor, TP53 mutation status and expression subtypes in sporadic breast cancer. Mol Oncol. 5:61–76. 2011. View Article : Google Scholar
22	Hotomi M, Sugitani I, Toda K, Kawabata K and Fujimoto Y: A novel definition of extrathyroidal invasion for patients with papillary thyroid carcinoma for predicting prognosis. World J Surg. 36:1231–1240. 2012. View Article : Google Scholar : PubMed/NCBI