BACKGROUND: Hormonal differences are hypothesized to contribute to the approximately ≥2-fold higher thyroid cancer incidence rates among women compared with men worldwide. Although thyroid cancer cells express estrogen receptors and estrogen has a proliferative effect on papillary thyroid cancer (PTC) cells in vitro, epidemiologic studies have not found clear associations between thyroid cancer and female hormonal factors. We hypothesized that polymorphic variation in hormone pathway genes is associated with the risk of developing papillary thyroid cancer. METHODS: We evaluated the association between PTC and 1151 tag single nucleotide polymorphisms (SNPs) in 58 candidate gene regions involved in sex hormone synthesis and metabolism, gonadotropins, and prolactin in a case-control study of 344 PTC cases and 452 controls, frequency matched on age and sex. Odds ratios and p-values for the linear trend for the association between each SNP genotype and PTC risk were estimated using unconditional logistic regression. SNPs in the same gene region or pathway were aggregated using adaptive rank-truncated product methods to obtain gene region-specific or pathway-specific p-values. To account for multiple comparisons, we applied the false discovery rate method. RESULTS: Seven SNPs had p-values for linear trend <0.01, including four in the CYP19A1 gene, but none of the SNPs remained significant after correction for multiple comparisons. Results were similar when restricting the dataset to women. p-values for examined gene regions and for all genes combined were ≥0.09. CONCLUSIONS: Based on these results, SNPs in selected hormone pathway genes do not appear to be strongly related to PTC risk. This observation is in accord with the lack of consistent associations between hormonal factors and PTC risk in epidemiologic studies.
BACKGROUND: Hormonal differences are hypothesized to contribute to the approximately ≥2-fold higher thyroid cancer incidence rates among women compared with men worldwide. Although thyroid cancer cells express estrogen receptors and estrogen has a proliferative effect on papillary thyroid cancer (PTC) cells in vitro, epidemiologic studies have not found clear associations between thyroid cancer and female hormonal factors. We hypothesized that polymorphic variation in hormone pathway genes is associated with the risk of developing papillary thyroid cancer. METHODS: We evaluated the association between PTC and 1151 tag single nucleotide polymorphisms (SNPs) in 58 candidate gene regions involved in sex hormone synthesis and metabolism, gonadotropins, and prolactin in a case-control study of 344 PTC cases and 452 controls, frequency matched on age and sex. Odds ratios and p-values for the linear trend for the association between each SNP genotype and PTC risk were estimated using unconditional logistic regression. SNPs in the same gene region or pathway were aggregated using adaptive rank-truncated product methods to obtain gene region-specific or pathway-specific p-values. To account for multiple comparisons, we applied the false discovery rate method. RESULTS: Seven SNPs had p-values for linear trend <0.01, including four in the CYP19A1 gene, but none of the SNPs remained significant after correction for multiple comparisons. Results were similar when restricting the dataset to women. p-values for examined gene regions and for all genes combined were ≥0.09. CONCLUSIONS: Based on these results, SNPs in selected hormone pathway genes do not appear to be strongly related to PTC risk. This observation is in accord with the lack of consistent associations between hormonal factors and PTC risk in epidemiologic studies.
Authors: Christopher S Carlson; Michael A Eberle; Mark J Rieder; Qian Yi; Leonid Kruglyak; Deborah A Nickerson Journal: Am J Hum Genet Date: 2003-12-15 Impact factor: 11.025
Authors: Stefan Lönn; Parveen Bhatti; Bruce H Alexander; Marbin A Pineda; Michele M Doody; Jeffery P Struewing; Alice J Sigurdson Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-01 Impact factor: 4.254
Authors: Gila Neta; Alina V Brenner; Erich M Sturgis; Ruth M Pfeiffer; Amy A Hutchinson; Briseis Aschebrook-Kilfoy; Meredith Yeager; Li Xu; William Wheeler; Michael Abend; Elaine Ron; Margaret A Tucker; Stephen J Chanock; Alice J Sigurdson Journal: Carcinogenesis Date: 2011-06-03 Impact factor: 4.944
Authors: Hannah P Yang; Jesus Gonzalez Bosquet; Qizhai Li; Elizabeth A Platz; Louise A Brinton; Mark E Sherman; James V Lacey; Mia M Gaudet; Laurie A Burdette; Jonine D Figueroa; Julia G Ciampa; Jolanta Lissowska; Beata Peplonska; Stephen J Chanock; Montserrat Garcia-Closas Journal: Carcinogenesis Date: 2010-01-06 Impact factor: 4.944
Authors: Alice J Sigurdson; Michele Morin Doody; R Sowmya Rao; D Michal Freedman; Bruce H Alexander; Michael Hauptmann; Aparna K Mohan; Shinji Yoshinaga; Deirdre A Hill; Robert Tarone; Kiyohiko Mabuchi; Elaine Ron; Martha S Linet Journal: Cancer Date: 2003-06-15 Impact factor: 6.860
Authors: Kai Yu; Qizhai Li; Andrew W Bergen; Ruth M Pfeiffer; Philip S Rosenberg; Neil Caporaso; Peter Kraft; Nilanjan Chatterjee Journal: Genet Epidemiol Date: 2009-12 Impact factor: 2.135
Authors: Alice J Sigurdson; Alina V Brenner; James A Roach; Lilia Goudeva; Jörg A Müller; Kai Nerlich; Christoph Reiners; Robert Schwab; Liliane Pfeiffer; Melanie Waldenberger; Melissa Braganza; Li Xu; Erich M Sturgis; Meredith Yeager; Stephen J Chanock; Ruth M Pfeiffer; Michael Abend; Matthias Port Journal: Carcinogenesis Date: 2016-04-28 Impact factor: 4.944