Carcinogenesis Advance Access originally published online on November 21, 2003
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Carcinogenesis, Vol. 25, No. 3, 369-373,
March 2004
Carcinogenesis vol.25 no.3 © Oxford University Press 2004; all rights reserved.
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Risk of non-medullary thyroid cancer influenced by polymorphic variation in the thyroglobulin gene
1 Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK, 2 Department of Medicine, Royal Marsden Hospital NHS Trust, SM2 5TT, UK, 3 Cancer Prevention Center, Sir MB Davis—Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2, Canada, 4 Division of Medical Genetics, Department of Medicine, Research Institute of the McGill University Montreal General Hospital Research Institute, Montreal, Quebec, H3G 1A2, Canada, 5 Department of Clinical Oncology, Royal Marsden Hospital NHS Trust, SM2 5NG, UK, 6 Department of Nuclear Medicine, Guy's and St Thomas' Hospital, London SE1 9RT, UK and 7 Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, H2W 1S6, Canada
Benign thyroid disorders are strong risk factors for non-medullary thyroid cancer (NMTC). Germline variation in Tg (thyroglobulin) and TSHR (thyroid stimulating hormone receptor) confers an increased risk of benign thyroid disorders. To explore the hypothesis that polymorphic variation in these genes affects the risk of NMTC we compared the frequency of TgQ2511R, TSHR-P52T and TSHR-D727E genotypes in two series of NMTC cases and controls (group 1, Canadian 102 cases and 102 controls; group 2, British 202 cases and 298 controls). No significant association was seen with TSHR-P52T and TSHR-D727E genotypes and risk of NMTC. However, the frequency of the R-allele of TgQ2511R was over represented in NMTC cases in both study populations. The odds ratios associated with hetero- and homozygosity for the R-allele were 1.6 (95% confidence interval, 1.1–2.5) and 2.0 (95% confidence interval, 1.2–3.3), respectively. Although the risk of NMTC associated with the TgQ2511R R-allele is modest, its high prevalence in the general population suggests it may make a significant contribution to the incidence of NMTC.
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