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), GSK3ß (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 GSK3ß 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 GSK3ß rs9879992 were significantly associated with oral cancer after 1000 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 (p1000permutation<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.
Subject(s)
Breast Neoplasms/genetics , Cleft Palate/genetics , Genetic Predisposition to Disease , Mouth Neoplasms/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Alleles , Brazil , Carcinoma, Squamous Cell/genetics , Case-Control Studies , Female , Genotype , Glycogen Synthase Kinase 3 beta/genetics , Humans , Interferon Regulatory Factors/genetics , Logistic Models , Male , Middle Aged , Mutation , Regression Analysis , Risk Factors , Wnt Proteins/geneticsABSTRACT
BACKGROUND: Epidemiological studies have indicated a higher incidence of breast and gastric cancer in patients with nonsyndromic cleft lip with or without cleft palate (NSCL ± P) and their relatives, which can be based on similar genetic triggers segregated within family with NSCL ± P. METHODS: This multicenter study evaluated the association of 9 single nucleotide polymorphisms (SNP) in AXIN2 and CDH1, representing genes consistently altered in breast and gastric tumors, with NSCL ± P in 223 trios (father, mother and patient with NSCL ± P) by transmission disequilibrium test (TDT). RESULTS: Our results showed that the minor A allele of rs7210356 (p = 0.01) and the T-G-G-A-G haplotype formed by rs7591, rs7210356, rs4791171, rs11079571 and rs3923087 SNPs (p = 0.03) in AXIN2 were significantly under-transmitted to patients with NSCL ± P. In CDH1 gene, the C-G-A-A and A-G-A-G haplotypes composed by rs16260, rs9929218, rs7186053 and rs4783573 polymorphisms were respectively over-transmitted (p = 0.01) and under-transmitted (p = 0.008) from parents to the children with NSCL ± P. CONCLUSIONS: The results suggest that polymorphic variants in AXIN2 and CDH1 may be associated with NSCL ± P susceptibility, and reinforce the putative link between cancer and oral clefts.
