Polymorphisms associated with oral clefts as potential susceptibility markers for oral and breast cancer

Publication date: Available online 14 December 2018

Source: Archives of Oral Biology

Author(s): Edimilson Martins de Freitas, Renato Assis Machado, Edilmar de Moura Santos, Felipe Rodrigues de Matos, Hébel Cavalcanti Galvão, Priscila Bernardina Miranda Soares, Roseana de Almeida Freitas, Hercílio Martelli

ABSTRACT

Objective

To evaluate the association of single nucleotide polymorphisms (SNPs) in genes/loci consistently altered in nonsyndromic oral clefts in patients with oral and breast cancer in a Brazilian population.

Design

This case-control study evaluated the association of SNPs in IRF6 (rs642961), WNT3A (rs708111), GSK3β (rs9879992), 8q24 (rs987525) and WNT11 (rs1533767), representing regions consistently identified as of susceptibility for oral clefts, with oral cancer (oral squamous cell carcinoma) and breast cancer. Logistic regression analyses were used for confounding adjustments, and p values ≤0.01 were considered statistically significant (Bonferroni correction = 0.05 / 5 polymorphic markers).

Results

The minor G allele of rs9879992 in GSK3β was associated with oral cancer risk (p = 0.02), whereas rs1533767 in WNT11 showed a protective effect against it (p = 0.04). Several SNP-SNP interactions containing GSK3β rs9879992 were significantly associated with oral cancer after 1,000 permutation test. To breast cancer, the A allele of rs987525 was associated with increase risk in early stage (p = 0.02) and SNP-SNP interactions involving the 5 SNPs were significantly observed, with the most significant interaction among rs708111, rs1533767, rs9879992 and rs642961 (p_{1000permutation}<0.001).

Conclusion

Our results reveal associations of SNPs consistently altered in oral cleft with oral and breast cancer risk, raising interesting possibilities to identify risk markers for those tumors.

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