GWAS of susceptibility loci for oral cavity and pharyngeal CA. And GUESS WHO shows up ???

Authors (see attached report) conducted a very exciting genome-wide association study (GWAS) of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. They detected eight significantly associated loci (P <5 × 10–8) –– seven of which never before reported as being associated with tumors at these epithelial cell-types.

 

Oral and pharyngeal cancers, combined, were associated with loci at 6p21.32 (HLA-DQB1), 10q26.13 (LHPP) and 11p15.4 (OR52N2TRIM5). Oral cancer was associated with two new regions –– 2p23.3 (GPN1) and 9q34.12 (LAMC3), and with two already established cancer-related loci –– 9p21.3 (CDKN2B-AS1) and 5p15.33 (CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation methods showed a protective association with the class II haplotype HLA-DRB1*13:01–HLA-DQA1*0103–HLA-DQB1*06:03 [odds ratio (OR) = 0.59, P = 2.7 × 10–9). Stratified analyses –– on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status –– indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10–6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

It is unfortunate that the Abstract does not even MENTION the highly significant correlation of ADH1B with these types of cancers –– at 4q23 for oral cancer and pharyngeal cancer combined (P = 2.3 × 10–15), for oral cancer alone (P = 1.1 × 10–9), and for pharyngeal cancer alone (P = 8.5 × 10–9). Toward the end of the article, authors DO mention that association of these cancer types with ADH1B has been reported previously (metadata analysis of 29 studies); however, this study (more than 12,500 cases plus controls in three geographic regions of the world) to me represents a very compelling, robust beautiful study, and I believe ADH1B should at least have been mentioned.

Nat Genet Dec 2o16; 48: 1544-1550

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