Contribution of personalized Cyclin D1 genotype to triple negative breast cancer risk

Abstract

Aim: Cell cycle regulator cyclin D1 (CCND1) is a pivotal regulator for G1/S phase transition, playing a critical part in initiation of carcinogenesis. Triple negative breast cancer comprises a very heterogeneous group of cancer cells, but little is known about what is wrong in the genome of these patients. This study investigated contribution of CCND1 genotype to individual triple negative breast cancer susceptibility.Materials: In all, 2464 native Taiwan subjects consist of 1232 breast cancer cases and 1232 controls were enrolled in a hospital-based, case-control study. CCND1 A870G (rs9344) genotyping was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Risk-stratified analyses correlated genotype and age-related characteristics of breast cancer subgroups.Results: No significant difference was found between patient and control groups in distribution of genotypic and allelic frequencies in CCND1 genotype, yet CCND1 A870G (rs9344) GG genotype was far less prevalent in breast cancer patients younger than 55 years (OR=0.62, 95%CI=0.43–0.89, P=0.0362), with first menarche earlier than 12.2 years (OR=0.61, 95% CI=0.42–0.87, P=0.0241), with menopause earlier than 49.0 years (OR=0.57, 95%CI=0.39–0.82, P=0.0093), or showing triple-negative breast cancer (OR=0.28, 95%CI=0.13–0.62, P=0.0006). Such valuable findings suggest CCND1 A870G (rs9344) as a predictive marker for triple negative breast cancer in Taiwanese women; the authors sincerely hope these help us fight the toughest subtype in clinical management.

Risk of Breast Cancer in Patients with Thyroid Cancer Receiving or Not Receiving 131I Treatment: A Nationwide Population-Based Cohort Study

“…Multiple primary tumors account for 13.1% of cancers in men and 13.7% of cancers in women, and all cancer survivors have a 2-fold-greater probability of developing a second primary cancer than cancer-free people. The cooccurrence of multiple malignancies could be random or associated with risk factors such as an environmental or genetic predisposition and therapy-related effects (16,23,24). Thyroid remnants ablation is not necessary in patients with low-risk thyroid cancer.…”

Constitutive activation of STAT3 in breast cancer cells: A review

“…One of the functions of Survivin (encoded by BIRC5 gene) is to inhibit caspase activation, leading to negative regulation of apoptosis or programmed cell death . A direct evidence for the correlation between STAT3 activation and elevated Cyclin D1 protein (encoded by CCND1 gene) expression in primary breast tumors and BC‐derived cell lines was reported . To control cell cycle progression from G1, D cyclins assemble with the cyclin‐dependent kinases 4/6 (CDK4/6), phosphorylate substrates such as retinoblastoma protein (Rb), release E2F transcription factor and promote entry of cells to S‐phase .…”

“…79 A direct evidence for the correlation between STAT3 activation and elevated Cyclin D1 protein (encoded by CCND1 gene) expression in primary breast tumors and BC-derived cell lines was reported. 80,81 To control cell cycle progression from G1, D cyclins assemble with the cyclin-dependent kinases 4/6 (CDK4/6), phosphorylate substrates such as retinoblastoma protein (Rb), release E2F transcription factor and promote entry of cells to S-phase. 80 Twistrelated protein 1 (Twist1) is a basic helix-loop-helix (bHLH) transcription factor encoded by the TWIST gene in humans.…”

The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk

“…In recent years, the Terry Fox Cancer Research group in the China Medical University and Hospital has been continuously devoted to the genotyping work of breast cancer in Taiwan, and their efforts have provided some potential predictive biomarkers such as G-1394T (rs 6869366) in XRCC4 [ 14 ], K589E (rs1047840) in EXO1 [ 15 ], G-1401T (rs828907) in XRCC5 [ 16 ], Asp312Asn (rs1799793) in XPD [ 17 ], rs189037 in ATM [ 18 ], G14713A and T29107A in CAV-1 [ 19 ], C-802G (rs14133) in CRYAB [ 20 ], C677T (rs1801133) in MTHFR [ 21 ], and G-765C (rs20417) in COX-2 [ 10 ]. The systematic analyses of clinicopathologic statuses have extended our understanding of the contributions of genotypes to TNBC [ 9 , 22 ]. It goes without saying that it is very meaningful to identify those potential predictive markers for breast cancer and their subtypes, such as TNBC.…”