The 8q24 rs6983267G variant is associated with increased thyroid cancer risk

Abstract

The G allele of the rs6983267 single nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in thyroid cancer susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3,067 cases and 8,575 controls. We detected significant associations between rs6983267G and thyroid cancer in the British Isles (Odds Ratio, OR= 1.19, 95% confidence interval, CI: 1.11–1.27, P= 4.03 × 10−7), Japan (OR= 1.20, 95% CI: 1.03–1.41, P= 0.022) and a borderline significant association of similar effect direction and size in Colombia (OR= 1.19, 95% CI: 0.99–1.44, P= 0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5,484 cases and 12,594 controls, confirmed the association between rs6983267G and thyroid cancer (P= 1.23 × 10−7, OR= 1.13, 95% CI: 1.07–1.18). Our results therefore support the notion that rs6983267G is a bona fide thyroid cancer risk variant that increases the risk of disease by ~13%.

Association between 8q24 rs6983267 polymorphism and cancer susceptibility: a meta-analysis involving 170,737 subjects

“…One study [ 52 ] was treated as 9 independent case groups because nine cancer types were studied. Moreover, we retrieved 25 separated investigations from 9 articles [ 8 , 10 , 39 , 42 , 54 , 61 , 74 , 83 , 88 ]. Finally, a total of 78 separate studies involving 73,996 cases and 96,741 controls were included in our meta-analysis.…”

Biologic and Clinical Perspectives on Thyroid Cancer

“…Recently, a germline variant of HABP2 was shown to be associated with papillary thyroid carcinoma in an extended kindred, 20 although the validity of this finding has been questioned. 21,22 …”

Clinical features of Hispanic thyroid cancer cases and the role of known genetic variants on disease risk

“… [9] Recent genome-wide association (GWA) and candidate studies in Europeans have identified TC risk alleles on chromosomes 2q35 (rs966423), 8p12 (rs2439302), 8q24 (rs6983267), 9q22 (rs965513), and 14q13 (rs944289 and rs116909374). [ 10 11 12 13 ] The effects of some of these known TC variants have been tested in independent populations and so far, most of these variants have been replicated in populations of British, [14] Japanese, [15] and Chinese[ 16 17 ] ancestry. However, to our knowledge, these known single nucleotide polymorphisms (SNPs) have not been comprehensively tested in any South American population.…”