TY - JOUR
T1 - The HABP2 G534E variant is an unlikely cause of familial non-medullary thyroid cancer
AU - Sahasrabudhe, Ruta
AU - Stultz, Jacob
AU - Williamson, John
AU - Lott, Paul
AU - Estrada, Ana
AU - Bohorquez, Mabel
AU - Palles, Claire
AU - Polanco-Echeverry, Guadalupe
AU - Jaeger, Emma
AU - Martin, Lynn
AU - Magdalena Echeverry, Maria
AU - Tomlinson, Ian
AU - Carvajal-Carmona, Luis G
AU - TCUKIN Consortium
PY - 2016/3/1
Y1 - 2016/3/1
N2 - CONTEXT: A recent study reported the non-synonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial non-medullary thyroid cancer (NMTC).OBJECTIVE: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multi-center population based study of NMTC cases from the British Isles.DESIGN AND SETTING: A case-control analysis of rs7080536 genotypes was performed using 2,105 TCUKIN cases and 5,172 UK controls.PARTICIPANTS: Cases comprised 2,105 NMTC cases. Patients sub-groups with papillary (N=1,056), follicular (N=691) and Hurthle cell (N=86) TC cases were studied separately. Controls comprised 5,172 individuals from the 1958 Birth Cohort (58C) and the National Blood Donor Service (NBS) study. The controls had previously been genotyped using genome-wide SNP arrays by the Wellcome Trust Case Control Consortium study.OUTCOME: Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression.RESULTS: The frequency of HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (OR=0.896, 95% CI: 0.746-1.071, P=0.233). We also failed to detect an association between HABP2 G534E and cases with papillary (1056 cases, G534E frequency= 3.5%, OR=0.74, P=0.017), follicular (691 cases, G534E frequency= 4.7%, OR=1.00, P=1.000) or Hurthle cell (86 cases, G534E frequency= 6.3%, OR=1.40, P=0.279) histology.CONCLUSIONS: We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC and additional data are required before using this variant in NMTC risk assessment.
AB - CONTEXT: A recent study reported the non-synonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial non-medullary thyroid cancer (NMTC).OBJECTIVE: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multi-center population based study of NMTC cases from the British Isles.DESIGN AND SETTING: A case-control analysis of rs7080536 genotypes was performed using 2,105 TCUKIN cases and 5,172 UK controls.PARTICIPANTS: Cases comprised 2,105 NMTC cases. Patients sub-groups with papillary (N=1,056), follicular (N=691) and Hurthle cell (N=86) TC cases were studied separately. Controls comprised 5,172 individuals from the 1958 Birth Cohort (58C) and the National Blood Donor Service (NBS) study. The controls had previously been genotyped using genome-wide SNP arrays by the Wellcome Trust Case Control Consortium study.OUTCOME: Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression.RESULTS: The frequency of HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (OR=0.896, 95% CI: 0.746-1.071, P=0.233). We also failed to detect an association between HABP2 G534E and cases with papillary (1056 cases, G534E frequency= 3.5%, OR=0.74, P=0.017), follicular (691 cases, G534E frequency= 4.7%, OR=1.00, P=1.000) or Hurthle cell (86 cases, G534E frequency= 6.3%, OR=1.40, P=0.279) histology.CONCLUSIONS: We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC and additional data are required before using this variant in NMTC risk assessment.
KW - Journal Article
U2 - 10.1210/jc.2015-3928
DO - 10.1210/jc.2015-3928
M3 - Article
C2 - 26691890
SN - 0021-972X
VL - 10
SP - 1098
EP - 1103
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 3
ER -
