Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma.

BACKGROUND: In recent years, morbidity and mortality from colorectal cancer have increased. Colorectal adenoma is the main precancerous lesion. Understanding the pathogenesis of colorectal adenoma will help to improve the early diagnosis rate of colorectal cancer. METHODS: In this case-control study, we focused on three single nucleotide polymorphisms (SNPs) in genes SLC8A1 (rs4952490), KCNJ1 (rs2855798), and SLC12A1 (rs1531916). We analyzed 207 colorectal adenoma patients (112 high-risk cases and 95 low-risk cases) and 212 control subjects by Sanger sequencing. A food frequency questionnaire (FFQ) was used to survey demographic characteristics and dietary nutrition. RESULTS: In the overall analysis, the results suggested that the AA+AG and AG genotype carriers of rs4952490 had a 73.1% and 78% lower risk of colorectal adenoma compared to GG genotype carriers, respectively. However rs2855798 and rs1531916 were not associated with the incidence of colorectal adenoma. Additionally, stratified analysis showed that rs4952490 AA+AG and AG genotypes had a protective effect against low-risk colorectal adenoma in patients aged ≤ 60 years old who were non-smokers. We also observed that when calcium intake was higher than 616 mg/d and patients carried at least one gene with variant alleles there was a protective effect against low-risk colorectal adenoma. CONCLUSIONS: Interactions between dietary calcium intake and calcium reabsorption genes may affect the occurrence and development of colorectal adenoma.

Correlation between Metabolite of Prostaglandin E2 and the incidence of colorectal adenomas.

Colorectal cancer is a common malignancy, and the incidence and mortality rates continue to rise. An important factor in the emergence of inflammation-induced colorectal carcinogenesis is elevated cyclooxygenase-2. Prostaglandin E2 (PGE2) over-production is frequently equated with cyclooxygenase-2 gene over-expression. PGE2 can be assessed by measuring the level of prostaglandin's main metabolite, PGE-M, in urine. Colorectal adenoma is a precancerous lesion that can lead to colorectal cancer. We conducted research to evaluate the association between urinary levels of the PGE-M and the risk of colorectal adenomas. In a western Chinese population, we identified 152 cases of adenoma and 152 controls patients without polyps. Adenoma cases were categorized into control, low-risk and high-risk groups. There was no significant change in PGE-M levels, between the control group and the low-risk adenoma group. In the high-risk group, the PGE-M levels were 23% higher than the control group. When compared to people with the lowest urine PGE-M levels (first quartile), people with greater urinary PGE-M levels had a higher chance of developing high-risk colorectal adenomas, with an adjusted odds ratio (95% CI) of 1.65 (0.76-3.57) in the fourth quartile group, (p= 0.013). We conclude urinary PGE-M is associated with the risk of developing high-risk adenomas. Urinary PGE-M level may be used as a non-invasive indicator for estimating cancer risk.

Clinical considerations of CDK4/6 inhibitors in HER2 positive breast cancer.

Deregulation of cell cycles can result in a variety of cancers, including breast cancer (BC). In fact, abnormal regulation of cell cycle pathways is often observed in breast cancer, leading to malignant cell proliferation. CDK4/6 inhibitors (CDK4/6i) can block the G1 cell cycle through the cyclin D-cyclin dependent kinase 4/6-inhibitor of CDK4-retinoblastoma (cyclinD-CDK4/6-INK4-RB) pathway, thus blocking the proliferation of invasive cells, showing great therapeutic potential to inhibit the spread of BC. So far, three FDA-approved drugs have been shown to be effective in the management of advanced hormone receptor positive (HR+) BC: palbociclib, abemaciclib, and ribociclib. The combination strategy of CDK4/6i and endocrine therapy (ET) has become the standard therapeutic regimen and is increasingly applied to advanced BC patients. The present study aims to clarify whether CDK4/6i can also achieve a certain therapeutic effect on Human epidermal growth factor receptor 2 positive (HER2+) BC. Studies of CDK4/6i are not limited to patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced BC, but have also expanded to other types of BC. Several pre-clinical and clinical trials have demonstrated the potential of CDK4/6i in treating HER2+ BC. Therefore, this review summarizes the current knowledge and recent findings on the use of CDK4/6i in this type of BC, and provides ideas for the discovery of new treatment modalities.

Prognostic role of radiotherapy in low-risk elderly breast cancer patients after breast-conserving surgery: a cohort study.

Background: Previous research suggested that radiotherapy (RT) had a small absolute benefit in patients with low-risk breast cancer over the age of 65. To reduce the patient's treatment burden and cost, as well as the damage to normal tissue, this study sought to explore the prognostic role of RT after breast-conserving surgery (BCS) in elderly patients. Methods: Patients who were aged ≥65 years, stage T1N0M0, and estrogen receptor/progesterone receptor positive (ER+/PR+) were included in this study. Age, marital status, histology, race, grade, human epidermal growth factor receptor 2 (HER2), subtype, treatment method, and survival were also collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. We compared overall survival (OS) and breast cancer-specific survival (BCSS) before and after propensity score matching (PSM) in the patients who underwent BCS with or without RT. Kaplan-Meier method and Cox proportional hazards regression analyses were used in our study. Results: The data of 3,623 patients were analyzed in this study. Among them, 2,851 (78.69%) patients had received RT. The multivariate analyses before PSM showed that RT resulted in better OS [hazard ratio (HR) 0.51, 95% confidence interval (CI): 0.42-0.62, P<0.001], and BCSS (HR 0.40, 95% CI: 0.27-0.58, P<0.001). The multivariate analyses after PSM (n=1,538) confirmed that patients who received RT (n=769) had a longer survival time than those who did not (n=769) (OS: HR 0.73, 95% CI: 0.57-0.95, P=0.018; and BCSS: HR 0.57, 95% CI: 0.35-0.93, P=0.025). The survival analysis showed that patients receiving RT had a better OS (P=0.028) and BCSS (P=0.016) than those who did not receive RT. However, there were no significant differences in patients' OS and BCSS with or without RT across the different age subgroups (P>0.05). Conclusions: In our study, patients who received RT had a longer survival time. However, the age subgroup analysis showed that RT did not have any survival benefit in elderly patients with T1N0M0 and ER+/PR+ breast cancer. Furthermore, at the age of 65-69 years, the P value for OS approached 0.05, which suggests that the decision to administer RT in this patient group should be made based on each patient's condition.