Genotypes and Haplotypes in the AXIN2 and TCF7L2 Genes are Associated With Susceptibility and With Clinicopathological Characteristics in Breast Cancer Patients.

Background: Breast cancer is a multifactorial disease whose genetic susceptibility is related to polymorphic variants of cell proliferation and migration pathways. Variants in AXIN2 and TCF7L2 in the Wnt-ß catenin pathway have been associated with different types of cancer; however, little is known about its role in breast cancer. This study tests the hypothesis of links between AXIN2 rs1133683 and rs2240308, and TCF7L2 rs7903146 and rs12255372 variants in breast cancer. Methods: Peripheral blood samples were obtained from 404 women (202 patients and 202 control females). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology was used to identify the gene variants. Results: The AXIN2 rs2240308 (C > T), and TCF7L2 rs7903146 (C > T) and rs12255372 (G > T) variants were associated with breast cancer and with age, TNM stage, and histologic-molecular subtype (p = 0.001). Likewise, the haplotype T-T in the TCF7L2 gene (rs7903146-rs12253372) was significantly related with breast cancer (OR = 2.66, 95%, CI = 1.64-4.30, p = 0.001). Conclusion: Our data show a link between AXIN2 rs2240308 and TCF7L2 rs7903146 and rs12255372 variants in breast cancer, and speculate this may be important in pathogenesis.

Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population

Abstract Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease. Objectives: The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. Material and Methods: This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population. Conclusion: The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.

Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population.

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.