TS 1494del6 polymorphism and increased risk of developing breast cancer
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, cilt.9, sa.6, ss.11756-11763, 2016 (SCI-Expanded)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 9 Sayı: 6
- Basım Tarihi: 2016
- Dergi Adı: INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.11756-11763
- Anahtar Kelimeler: Breast cancer, thymidylate synthase, TS 1494del6, polymorphism, THYMIDYLATE-SYNTHASE POLYMORPHISMS, SQUAMOUS-CELL CARCINOMA, COLORECTAL-CANCER, GASTRIC-CANCER, FOLATE INTAKE, LUNG-CANCER, GENE, ASSOCIATION, REGION, SUSCEPTIBILITY
- Akdeniz Üniversitesi Adresli: Evet
Özet
Thymidylate synthase (TS) is a critical enzyme involved in folate metabolism and catalyses reductive methylation of deoxyuridylate to thymidylate, which is the essential precursor for DNA. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, DNA synthesis and repair. These functions may provide insight individual susceptibility to cancer. We investigated the probable effects of TS 1494del6 polymorphism on the risk of developing breast cancer. Genotypes of 298 cases and 300 controls were determined by use of PCR-RFLP. Variant -6 bp allele frequency was significantly higher in women with breast cancer than in controls (0.554 vs. 0.467; OR: 1.42, 95% CI: 1.13-1.78; P=0.003). The frequency of the -6 bp/-6 bp genotype was 12% in control group, while increased to 26.8% in women with breast cancer. Similarly, increased risk was observed for breast cancer of the -6 bp/-6 bp genotype compared with the +6 bp/+6 bp genotype (OR 2.59, 95% CI: 1.49-4.49; P=0.001). The risk increased in women with -6 bp/-6 bp genotype as well as age >= 55 (OR, 3.06; 95% CI: 1.15-8.07; P=0.024), BMI=25 kg/m(2) (OR, 2.81; 95% CI: 1.45-5.46; P=0.002), early menarche (before age 13 years) (OR, 3.52; 95% CI: 1.37-9.04; P=0.009), late age at first pregnancy (OR, 2.87; 95% CI: 1.77-4.64; P=0.0001), postmenopausal status (OR 5.44; 95% CI: 2.23-13.24; P=0.001), and negative smoking history (OR=3.09; 95% CI: 1.87-5.09; P=0.001). In conclusion, the TS 1494del6 polymorphism gene may contribute to an increased risk for breast cancer development, particularly in the presence of 55 years of age or older, high BMI, early age at menarche, late age at first pregnancy, postmenopausal status, and negative smoking history.