Risk Factors and Preventions of Breast Cancer Sun, Yi-Sheng; Zhao, Zhao; Yang, Zhang-Nv ...
International journal of biological sciences,
01/2017, Letnik:
13, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Breast cancer is the second leading cause of cancer deaths among women. The development of breast cancer is a multi-step process involving multiple cell types, and its prevention remains challenging ...in the world. Early diagnosis of breast cancer is one of the best approaches to prevent this disease. In some developed countries, the 5-year relative survival rate of breast cancer patients is above 80% due to early prevention. In the recent decade, great progress has been made in the understanding of breast cancer as well as in the development of preventative methods. The pathogenesis and tumor drug-resistant mechanisms are revealed by discovering breast cancer stem cells, and many genes are found related to breast cancer. Currently, people have more drug options for the chemoprevention of breast cancer, while biological prevention has been recently developed to improve patients' quality of life. In this review, we will summarize key studies of pathogenesis, related genes, risk factors and preventative methods on breast cancer over the past years. These findings represent a small step in the long fight against breast cancer.
The ketogenic diet (KD) is a high-fat, very-low-carbohydrate diet that triggers a fasting state by decreasing glucose and increasing ketone bodies, such as β-hydroxybutyrate (βHB). In experimental ...models and clinical trials, the KD has shown anti-tumor effects, possibly by reducing energy supplies to cells, which damage the tumor microenvironment and inhibit tumor growth. Here, we determined expression levels of genes encoding the ketolytic enzymes 3-hydroxybutyrate dehydrogenase 1 (BDH1) and succinyl-CoA: 3-oxoacid CoA transferase 1 (OXCT1) in 33 human cancer cell lines. We then selected two representative lines, HeLa and PANC-1, for in vivo examination of KD sensitivity in tumors with high or low expression, respectively, of these two enzymes. In mice with HeLa xenografts, the KD increased tumor growth and mouse survival decreased, possibly because these tumors actively consumed ketone bodies as an energy source. Conversely, the KD significantly inhibited growth of PANC-1 xenograft tumors. βHB added to each cell culture significantly increased proliferation of HeLa cells, but not PANCI-1 cells. Downregulation of both BDH1 and OXCT1 rendered HeLa cells sensitive to the KD in vitro and in vivo. Tumors with low ketolytic enzyme expression may be unable to metabolize ketone bodies, thus predicting a better response to KD therapy.
Elderly cancer patients are at particularly high risk for malnutrition because both the disease and the old age threaten their nutritional status. The Global Leadership Initiative on Malnutrition ...(GLIM) released new universal criteria for diagnosing and grading malnutrition, but the validation of these criteria in elderly cancer population is not well documented. Our objective was to investigate the application of the GLIM criteria in nutrition assessment and survival prediction in elderly cancer patients.
This retrospective cohort analysis was conducted on a primary cohort of 1192 cancer patients aged 65 years or older enrolled from a multi-institutional registry, and a validation cohort of 300 elderly cancer patients treated at the First Affiliated Hospital of Sun Yat-sen University. Patients considered at-risk for malnutrition based on the NRS-2002 were assessed using the GLIM criteria. The association between the nutritional status and patients' overall survival (OS) was then analyzed by the Kaplan–Meier method and a Cox model. A nomogram was also established that included additional independent clinical prognostic variables. To determine the predictive accuracy and discriminatory capacity of the nomogram, the C-index, receiver operating characteristic (ROC) curve and calibration curve were evaluated.
The percentage of patients considered “at-risk” for malnutrition was 64.8% and 67.3% for the primary and validation cohorts, respectively. GLIM-defined malnutrition was diagnosed in 48.4% of patients in the primary cohort and 46.0% in the validation cohort. In the primary cohort, patients at risk of malnutrition (NRS-2002 ≥ 3) showed a worse OS than those with a NRS-2002 < 3 (HR 1.34, 1.10–1.64; p = 0.003). Additionally, patients with GLIM-defined severe malnutrition (HR1.71, 1.37–2.14; p < 0.001) or moderate malnutrition (HR1.35, 1.09–1.66; p = 0.006) showed a significantly shorter OS compared to those without malnutrition. The nomogram incorporating the domains of the GLIM with other variables was accurate, especially for predicting the 1- and 2-year overall survival rates.
The GLIM criteria can be used in elderly cancer patients not only to assess malnutrition, but also to predict survival outcome. The nomogram developed based on the GLIM domains can provide a more accurate prediction of the prognosis than existing systems.
Porous elastomer has been used as the dielectric layer of capacitive pressure sensors to reduce the Young's modulus and improve the sensitivity. In this paper, influence of permittivity on the ...sensitivity of porous elastomer-based capacitive pressure sensors is investigated. By introducing metallic particles (silver nanoparticles) into porous elastomer (polydimethylsiloxane) to increase its permittivity, the sensitivity of the porous composite-based capacitive pressure sensor is improved by 101.5% in the low-to-medium pressure regime (0-100 kPa). The capacitive pressure sensor also shows high linearity, good durability, and high noise immunity. Due to its high sensitivity, an artificial hand based on the capacitive pressure sensor can detect tiny pressure changes induced by wrist pulse and derive pressure distribution on different phalanges.
Background
Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to ...assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown.
Methods
This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut‐off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC.
Results
In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow‐up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient‐years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244–2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC.
Conclusions
For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.
Background
Changes in body composition and systemic inflammation are important characteristics of cancer cachexia. This multi‐centre retrospective study aimed to explore the prognostic value of the ...combination of body composition and systemic inflammation in patients with cancer cachexia.
Methods
The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation, was defined as appendicular skeletal muscle index (ASMI) × serum albumin/neutrophil‐lymphocyte ratio. The ASMI was estimated according to a previously validated anthropometric equation. Restricted cubic splines were used to evaluate the relationship between mALI and all‐cause mortality in patients with cancer cachexia. Kaplan–Meier analysis and Cox proportional hazard regression analysis were used to evaluate the prognostic value of mALI in cancer cachexia. A receiver operator characteristic curve was used to compare the effectiveness of mALI and nutritional inflammatory indicators in predicting all‐cause mortality in patients with cancer cachexia.
Results
A total of 2438 patients with cancer cachexia were enrolled, including 1431 males and 1007 females. The sex‐specific optimal cut‐off values of mALI for males and females were 7.12 and 6.52, respectively. There was a non‐linear relationship between mALI and all‐cause mortality in patients with cancer cachexia. Low mALI was significantly associated with poor nutritional status, high tumour burden, and high inflammation. Patients with low mALI had significantly lower overall survival (OS) than those with high mALI (39.5% vs. 65.5%, P < 0.001). In the male population, OS was significantly lower in the low mALI group than in the high group (34.3% vs. 59.2%, P < 0.001). Similar results were also observed in the female population (46.3% vs. 75.0%, P < 0.001). mALI was an independent prognostic factor for patients with cancer cachexia (hazard ratio HR = 0.974, 95% confidence interval CI = 0.959–0.990, P = 0.001). For every standard deviation SD increase in mALI, the risk of poor prognosis for patients with cancer cachexia was reduced by 2.9% (HR = 0.971, 95%CI = 0.943–0.964, P < 0.001) in males and 8.9% (HR = 0.911, 95%CI = 0.893–0.930, P < 0.001) in females. mALI is an effective complement to the traditional Tumour, Lymph Nodes, Metastasis (TNM) staging system for prognosis evaluation and a promising nutritional inflammatory indicator with a better prognostic effect than the most commonly used clinical nutritional inflammatory indicators.
Conclusions
Low mALI is associated with poor survival in both male and female patients with cancer cachexia and is a practical and valuable prognostic assessment tool.
Background
Handgrip strength (HGS) is associated with poor clinical outcomes, including all‐cause, non‐cardiovascular, and cardiovascular mortalities. The published cut‐off points for HGS are mostly ...based on community populations from Western countries, lacking information on cancer patients from China. The objective of this study was to establish sex‐specific cut‐off points for Chinese cancer patients and investigate the effect of low HGS on cancer mortality.
Methods
We did a retrospective cohort study of patients who were diagnosed with malignant cancer from June 2012 to December 2018. HGS was measured using a hand dynamometer in 8257 cancer patients. Optimal stratification was used to solve threshold points. The hazard ratio (HR) of all cancer mortality and cancer‐specific mortality was calculated using Cox proportional hazard regression models.
Results
Among all participants, there were 3902 (47.3%) women and 4355 (52.7%) men. The median age was 58 years old. The cut‐off points of HGS to best classify patients with respect to time to mortality were <16.1 kg for women and <22 kg for men. Low HGS was associated with overall cancer mortality in both women and men HR = 1.339, 95% confidence interval (CI) = 1.170–1.531, P < 0.001; HR = 1.346, 95% CI = 1.176–1.540, P < 0.001, respectively. For specific cancer types, low HGS was associated with breast cancer (HR = 1.593, 95% CI = 1.230–2.063, P < 0.001) in women, and lung cancer (HR = 1.369, 95% CI = 1.005–1.866, P = 0.047) and colorectal cancer (HR = 1.399, 95% CI = 1.007–1.944, P = 0.045) in men.
Conclusions
On the basis of our sex‐specific cut‐off points, low HGS was strongly associated with cancer mortalities. These results indicate the usefulness of HGS measurement in routine clinical practice for improving patient assessments, cancer prognosis, and intervention.
The relationship between muscle and prognosis, especially that between muscle distribution across different body parts, and the related prognosis is not well established.
To investigate the ...relationship between muscle distribution and all-cause and cause-specific mortality and their potential modifiers.
Longitudinal cohort study. C-index, IDI, and NRI were used to determine the best indicator of prognosis. COX regression analysis was performed to explore the relationship between variables and outcomes. Interaction and subgroup analyses were applied to identify the potential modifiers.
A total of 5052 participants (weighted: 124,841,420) extracted from the NHANES 2003-2006 of median age 45 years and constituting 50.3% men were assessed. For validation, we included 3040 patients from the INSCOC cohort in China.
Muscle mass and distribution. KEY RESULTS: COX regression analysis revealed that upper limbs (HR = 0.41, 95% CI 0.33-0.51), lower limbs (HR = 0.54, 95% CI 0.47-0.64), trunk (HR = 0.71, 95% CI, 0.59-0.85), gynoid (HR = 0.47, 95% CI 0.38-0.58), and total lean mass (HR = 0.55, 95% CI 0.45-0.66) were all associated with the better survival of participants (P
< 0.001). The changes in the lean mass ratio of the upper and lower limbs and the lean mass ratio of the android and gynoid attenuated the protective effect of lean mass. Age and sex acted as potential modifiers, and the relationship between lean mass and the prognosis was more significant in men and middle-aged participants when compared to that in other age groups. Sensitive analyses depicted that despite lean mass having a long-term impact on prognosis (15 years), it has a more substantial effect on near-term survival (5 years).
Muscle mass and its distribution affect the prognosis with a more significant impact on the near-term than that on the long-term prognosis. Age and sex acted as vital modifiers.
Background
The obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail ...the mediation of obesity and inflammation on survival.
Methods
The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer. Survival analysis was performed using weighted (NHANES) or unweighted (INSCOC) Cox survival analyses. The normal BMI group was used as a reference for all comparisons. Systemic inflammation was defined as neutrophil‐to‐lymphocyte ratio (NLR) > 3. Model‐based causal mediation analysis was used to identify the mediators.
Results
A total of 52 270 (weighted population: 528506229) participants of the NHANES mean follow‐up times: 10.2 years; mean age (SD): 47 (19.16) years were included in the original cohort; and a total of 17 418 patients with cancer of INSCOC mean follow‐up times: 2.9 years; mean age (SD): 57.37 (11.66) years were included in the validation cohort. In the subgroups of all the participants, the obesity paradigm was more apparent in older participants and participants with disease HR (95% CI): age ≥ 65 years, 0.84 (0.76, 0.93); with cancer, 0.84 (0.71, 0.99); with CVD, 0.74 (0.65, 0.85). As aged, the protective effect of a high BMI on survival gradually increased and a high BMI showed the effect of a protective factor on older participants for obese II, HR (95% CI): young adults, 1.91 (1.40, 2.62); middle age, 1.56 (1.28, 1.91); old adults, 0.85 (0.76, 0.96). The aged‐related obesity paradigm in patients with cancer from the NHANES was verified in the INSCOC cohorts for obese, HR (95%CI): 0.65 (0.52, 0.81). The NLR is an important mediator of the effect of BMI on survival (proportion of mediation = 15.4%).
Conclusions
The obesity paradigm has a strong correlation with age. Relative to normal weight, obese in young people was association with higher all‐cause mortality, and obese in elderly people was not association with higher mortality. The protection of obesity is association with systemic inflammation.
The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5‐MTHF, is a critical but underexplored area in cancer research. This ...nested case–control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5‐MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82–0.99), while 5‐MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60–0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58–0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77–0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61–0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02–3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06–8.21). The impact of folate, THF, and 5‐MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.
What's new?
This study investigates the relationship between serum folate, THF, and 5‐MTHF levels and cancer risk, showing that folate's effect varies by genetic background and cancer type. Elevated THF levels correlate with decreased cancer risk. Importantly, the impact of 5‐MTHF on cancer risk depends on MTHFR C677T polymorphisms, offering protection in CC and CT genotypes but potentially increasing risk in TT genotypes. These findings highlight folate's complex role in cancer biology and the need for further research to understand these interactions.
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