HER2 Ile655Val and PTEN IVS4 polymorphisms in patients with breast cancer.

Although HER2/PTEN pathway is commonly disrupted in cancer, association of HER2 and PTEN polymorphisms with breast cancer (BC) remains controversial. We investigated the HER2 Ile655 Val and PTEN IVS4 polymorphisms in patients with BC in Turkish population. HER2 Ile655Val (rs 1136201) and PTEN IVS4 (rs 3830675) polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) in blood samples of 118 BC patients and 118 age-matched healthy controls. We found that the frequency of the Ile/Val genotype of HER2 Ile655Val gene was significantly higher in BC patients (p < 0.009; OR: 1,983 95 % CI: 1.181-3.328). The presence of ATCTT insertion (+/+) genotype at downstream of exon 4 in intron 4 of PTEN IVS4 gene was also associated with 1.83 fold decreased risk of BC development (p < 0.033; OR: 1.83, 95 % CI: 1.11-3.03). Analysis on clinico-pathological parameters showed neither HER2 Ile655Val nor PTEN IVS4 genotypes were not associated with any of the variables (p > 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population.

Association between PTEN IVS4 polymorphism and development of colorectal cancer in a Turkish population.

BACKGROUND: Phosphatase and tensin homolog (PTEN) is one of the most frequently mutated suppressor genes in human cancers. However, there are no data about the role of PTEN IVS4 polymorphism in development of colorectal cancer (CRC). The authors aimed to determine the role of PTEN IVS4 variants in the etiology of CRC. PATIENTS AND METHODS: A hospital-based case-control study was conducted in 203 patients with CRC (127 colon, 76 rectum) and 245 healthy controls. The frequencies of PTEN IVS4 (rs 3830675) genotypes were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The (-/-) genotype of PTEN IVS4 that absence of ATCTT insertion at downstream of exon 4 in intron 4 of PTEN gene was found to be associated with 1.55-fold increased risk of colon cancer (p < 0.005; OR: 1.55, 95% CI: 1.24 - 1.94) and 1.4-fold increased risk of rectum cancer (p < 0.005; OR: 1.4, 95% CI: 1.08 - 1.82). Subgroup analyses showed that PTEN IVS4 genotypes were not associated with any clinicopathological characteristics of patients with CRC (p > 0.05). CONCLUSION: The (-/-) genotype of PTEN IVS4 gene might be associated with increased risk for development of CRC in a Turkish population. Further studies will clarify the exact role of PTEN IVS4 polymorphism in the etiology of CRC.

Increased gastric cancer risk with PTEN IVS4 polymorphism in a Turkish population.

We aimed to investigate the association of the phosphatase and tensin homolog (PTEN) IVS4 polymorphism with a gastric cancer (GC) risk in the Turkish population. A hospital-based case-control study was conducted in 93 patients with GC, and 113 healthy controls. The PTEN IVS4 (rs no: 3830675) polymorphism was determined by using polymerase chain reaction-restriction fragment length polymorphism analysis. The PTEN IVS4 (-/-) genotype exhibited a significantly elevated risk for GC compared to controls (p<0.005; odds ratio: 1.6, 95% confidence interval: 1.19-2.14). Analyses on clinicopathological parameters showed that PTEN IVS4 genotypes were not associated with any of the variables of patients with GC (p>0.05). In conclusion, the PTEN IVS4 polymorphism might contribute to the development of GC in a Turkish population. Further studies, including comparison of the PTEN IVS4 polymorphism with plasma and tissue expressions of PTEN in larger study size groups will provide a further assessment of the PTEN IVS4 polymorphism in GC patients.