Thyroid Cancer Susceptibility and THRA1 and BAT-40 Repeats Polymorphisms

Abstract

Although genetic and environmental factors have been identified in the etiology of thyroid cancer, the specific genetic implications in sporadic thyroid tumors are poorly understood but, as in other common cancers, low-penetrance susceptibility genes are believed to be crucial in the tumorigenesis processes. Here, we have carried out a casecontrol study to investigate whether there is an association between THRA1 CA repeat or BAT-40 A repeat polymorphisms and thyroid cancer risk. The THRA1 repeat resides in the thyroid hormone receptor-a1 gene, which is associated with thyroid cancer and whose expression depends on the THRA1 repeat size. We also analyzed the BAT-40 repeat that maps to chromosome 1, a region known to be involved in thyroid cancer. This repeat is located in the 3-b-hydroxysteroid dehydrogenase gene that is associated with prostate cancer susceptibility. The THRA1 repeat was genotyped in 212 thyroid cancer patients and 141 controls of a Spanish population. From these individuals, 207 patients and 138 controls were also analyzed for the BAT-40 marker. No significant difference in the THRA1 allele distribution between patients and controls was found, although short alleles (<128 bp) might have some protective effect on thyroid cancer risk of carriers (odds ratio, 0.50; 95% confidence interval, 0.22-1.13; P = 0.094). By contrast, the BAT-40 allele distribution in patients was significantly different with respect to control (P = 0.035). Essentially, the difference were found in the genotypes involving the 111-to 115-bp allele range, which seem to be associated with a protective effect on thyroid cancer susceptibility in the studied population (odds ratio, 0.18; 95% confidence interval, 0.01-0.57; P = 0.02). Therefore, our results indicate that the BAT-40 containing region and to a less extend the thyroid hormone receptor-a1 gene are related to thyroid cancer susceptibility. To our knowledge, this is the first study reporting the identification of genetic factors for thyroid cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2005;14(3):638 -42)

Strong Association of Chromosome 1p12 Loci with Thyroid Cancer Susceptibility

“…We previously reported that the chromosome 1p12-13 was associated with thyroid cancer susceptibility in a case-control study using the microsatellite BAT-40 marker (13). In the present study, we have conducted a fine mapping of the susceptibility loci in this region by extending the analysis to an average distance of 2.4 Mb.…”

“…Thus, association studies aimed to identify genes for thyroid cancer risk have been recently published (9-12), although no specific genes for thyroid cancer susceptibility have yet been described. Our previous study, using the BAT-40 marker in a casecontrol study, indicated that the chromosome 1p12-13 is related to thyroid cancer susceptibility (13). Therefore, in the present study, we aimed to map the susceptibility loci on this region.…”

“…This type of study has recently emerged for thyroid cancer (7)(8)(9)(10)(11)(12), although no specific genetic factor for thyroid cancer susceptibility has yet been described. In a previous study, we have reported that the chromosome 1p12-13is related to thyroid cancer susceptibility (13). Several studies also indicate that this region undergoes many aberrations in different types of cancer (14)(15)(16)(17), which would suggest a certain role in cancer incidence.…”

Identifying a risk profile for thyroid cancer

“…A series of promising reports identifying polymorphisms in germline DNA have been published in an effort to delineate polygenic models of thyroid cancer susceptibility and prognosis (80)(81)(82). Such models are particularly interesting since they may help select individuals for specific chemopreventive interventions and determine which patients with nodules or with microcarcinomas are most likely to benefit from specific therapies.…”

TPO genetic variants and risk of differentiated thyroid carcinoma in two European populations

“…In these latter types of studies, a special interest should be given to SNPs within genes specifically involved in the thyroid function. In fact, although these studies are not frequently reported in the literature, SNPs within thyroglobulin ( TG ) and in thyroid‐related hormone receptors loci, such as THRA1 (thyroid hormone receptor type alpha‐1), are found associated with increased risks . Studies on genetic polymorphisms within other genes relevant for the thyroid functions, such as thyroperoxidase ( TPO ), are not reported.…”