Strong Association of Chromosome 1p12 Loci with Thyroid Cancer Susceptibility

Abstract

Several genes directly related to thyroid cancer development have been described; nevertheless, the genetic pathways of this tumorigenesis process are unknown. Together with environmental factors, susceptibility genes could have an important role in thyroid cancer. Our previous studies suggest that the chromosome 1p12-13 is related to thyroid cancer incidence. Here, we extend the analysis with a case-control association study in a Spanish population. Thus, six singlenucleotide polymorphisms were genotyped, covering 2.4 Mb of the 1p12-13 region. A statistically significant association between thyroid cancer incidence and the rs2145418 and rs4658973 polymorphisms was found (P < 0.0001). No association was detected for the other four polymorphisms studied. The rs2145418 marker showed a significant odds ratio of 5.0 [95% confidence interval (95% CI), 2.85-8.83] and 9.2 (95% CI, 4.50-21.6) for heterozygous and homozygous G-variant alleles, respectively. For rs4658973, the odds ratios were 0.40 (95% CI, 0.26-0.62) and 0.07 (95% CI, 0.03-0.18) for heterozygous and homozygous G-variant alleles, respectively. These markers map into the 1p12 region, and no linkage disequilibrium was found between them, indicating an independent relation of these polymorphisms with thyroid cancer susceptibility. Our data provide evidence of a strong association of the chromosome 1p12 with thyroid cancer risk, and it is the first study describing susceptibility loci for thyroid cancer in this region. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1499 -504)

Ribosomal 18 S RNA Processing by the IGF-I-responsive WDR3 Protein Is Integrated with p53 Function in Cancer Cell Proliferation

“…Individuals bearing a single nucleotide polymorphism (SNP) in the WDR3 gene locus have a strong association with thyroid cancer susceptibility (42). Deletions of the WDR3 gene locus have been detected in many malignant solid tumors of epithelial origin (26), and the unbalanced translocation t(1;3)(p12-13;q11) of the WDR3 locus has been detected in several brain tumors (43).…”

Common Variants of the Thyroglobulin Gene Are Associated with Differentiated Thyroid Cancer Risk

“…Interestingly, these regions contain thyroid differentiation genes FOXE1 and NKX2-1, respectively (4,5). Additional polymorphisms at 5q33 and 1p12 are also susceptibility loci for thyroid cancer (6,7), and more recently, the WDR3 gene that maps at 1p12 was found to be associated with the disease (8). In chromosome 8q24, three independent regions have been related to risk of different types of cancers, including thyroid cancer, but no known genes reside in that susceptibility region (9,10).…”

Thyroid tumorigenesis and molecular markers in thyroid cancer

“…Genetic predisposition to thyroid cancer has recently attracted a great deal of interest, and several publications [1][2][3][4][5][6][7][8] have been dedicated to this subject (Table 1). Between 5 and 10% of papillary thyroid cancers (PTCs) are known to be familial and likely have a multigenic component.…”

“…Finally, additional polymorphisms include an unknown region on 1p12 and the purinergic receptor on 12q24 [7,8]. Certainly, as genome-associated technology and computational biology become more advanced, our ability to identify genetic susceptibility loci for the development of thyroid cancer will markedly improve.…”