Relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer.

OBJECTIVE--To investigate the relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer as a possible explanation for socioeconomic differences in survival. DESIGN--Retrospective analysis of data from cancer registry and from pathology and biochemistry records. SETTING--Catchment areas of two large teaching hospitals in Glasgow. SUBJECTS--1361 women aged under 75 who had breast cancer diagnosed between 1980 and 1987. MAIN OUTCOME MEASURES--Tumour size, axillary lymph node status, histological grade, and oestrogen receptor concentration in relation to deprivation category of area of residence. RESULTS--There was no significant relation between socioeconomic deprivation and four pathological prognostic factors: 93 (32%) women in the most affluent group presented with tumours less than 20 mm in size compared with 91 (31%) women in the most deprived group; 152 (48%) of the most affluent group presented with negative nodes compared with 129 (46%) of the most deprived group; 23 (22%) of the most affluent group presented with grade I tumours compared with 12 (17%) of the most deprived group; and 142 (51%) of the most affluent group had a low oestrogen receptor concentration at presentation compared with 148 (52%) of the most deprived group. None of these differences was statistically significant. CONCLUSIONS--Differences in survival from breast cancer by socioeconomic deprivation category could not be accounted for by differences in tumour stage or biology. Other possible explanations, such as differences in treatment or in host response, should be investigated.     

The cancer secretome,current status and opportunities in the lung,breast and colorectal cancer context

Despite major improvements on the knowledge and clinical management, cancer is still a deadly disease. Novel biomarkers for better cancer detection, diagnosis and treatment prediction are urgently needed. Proteins secreted, shed or leaking from the cancer cell, collectively termed the cancer secretome, are promising biomarkers since they might be detectable in blood or other biofluids. Furthermore, the cancer secretome in part represents the tumor microenvironment that plays a key role in tumor promoting processes such as angiogenesis and invasion. The cancer secretome, sampled as conditioned medium from cell lines, tumor/tissue interstitial fluid or tumor proximal body fluids, can be studied comprehensively by nanoLC-MS/MS-based approaches. Here, we outline the importance of current cancer secretome research and describe the mass spectrometry-based analysis of the secretome. Further, we provide an overview of cancer secretome research with a focus on the three most common cancer types: lung, breast and colorectal cancer. We conclude that the cancer secretome research field is a young, but rapidly evolving research field. Up to now, the focus has mainly been on the discovery of novel promising secreted cancer biomarker proteins. An interesting finding that merits attention is that in cancer unconventional secretion, e.g. via vesicles, seems increased. Refinement of current approaches and methods and progress in clinical validation of the current findings are vital in order to move towards applications in cancer management. This article is part of a Special Issue entitled: An Updated Secretome.     

Associations between comorbidities and advanced stage diagnosis of lung,breast, colorectal,and prostate cancer: A systematic review and meta-analysis

Comorbidities and advanced stage diagnosis (ASD) are both associated with poorer cancer outcomes, but the association between comorbidities and ASD is poorly understood. We summarized epidemiological evidence on the association between comorbidities and ASD of selected cancers in a systematic review and meta-analysis. We searched PubMed and Web of Science databases up to June 3rd, 2021 for studies assessing the association between comorbidities and ASD of lung, breast, colorectal, or prostate cancer. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effects models. Also, potential variations in the associations between comorbidities and ASD by cancer type were investigated using random-effects meta-regression. Thirty-seven studies were included in this review, including 8,069,397 lung, breast, colorectal, and prostate cancer patients overall. The Charlson comorbidity index score was positively associated with ASD (stages III–IV) of breast cancer but was inversely associated with ASD of lung cancer (p_interaction = 0.004). Regarding specific comorbidities, diabetes was positively associated with ASD (OR = 1.17, 95%CI = 1.09–1.26), whereas myocardial infarction was inversely associated with ASD (OR = 0.84, 95%CI = 0.75–0.95). The association between renal disease and ASD differed by cancer type (p_interaction < 0.001). A positive association was found with prostate cancer (OR = 2.02, 95%CI = 1.58–2.59) and an inverse association with colorectal cancer (OR = 0.84, 95%CI = 0.70–1.00). In summary, certain comorbidities (e.g., diabetes) may be positively associated with ASD of several cancer types. It needs to be clarified whether closer monitoring for early cancer signs or screening in these patients is reasonable, considering the problem of over-diagnosis particularly relevant in patients with short remaining life expectancy such as those with comorbidities. Also, evaluation of the cost-benefit relationship of cancer screening according to the type and severity of comorbidity (rather than summary scores) may be beneficial for personalized cancer screening in populations with chronic diseases.     

Absence of association between N-acetyltransferase 2 acetylator status and colorectal cancer susceptibility: based on evidence from 40 studies

Background and Objectives

N-Acetyltransferase (NAT) 2 is an important enzyme involved in the metabolism of different xenobiotics, including potential carcinogens, whose phenotypes were reported to be related to individual susceptibility to colorectal cancer (CRC). However, the results remain conflicting. To assess the relationship between NAT2 phenotypes and CRC risk, we performed this meta-analysis.

Methods

A comprehensive literature search was conducted to identify all case-control or cohort studies of NAT2 acetylator status on the susceptibility of CRC by searching of PubMed and EMBASE, up to May 20, 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association.

Results

A total of over 40,000 subjects from 40 published literatures were identified by searching the databases. No significantly elevated CRC risk in individuals with NAT2 slow acetylators compared with fast acetylators was found when all studies pooled (OR = 0.95, 95% CI: 0.87–1.04, I² = 52.6%). While three studies contributed to the source of heterogeneity were removed, there was still null result observed (OR = 0.96, 95% CI: 0.90–1.03, P = 0.17 for heterogeneity, I² = 17.8%). In addition, we failed to detect any associations in the stratified analyses by race, sex, source of controls, smoking status, genotyping methods or tumor localization. No publication bias was observed in this study.

Conclusions

This meta-analysis suggests that the NAT2 phenotypes may not be associated with colorectal cancer development.     

Clinical relevance of Ephs and ephrins in cancer: lessons from breast, colorectal, and lung cancer profiling

Pre-clinical studies provide compelling evidence that members of the Eph family of receptor tyrosine kinases and their ephrin ligands promote tumor growth, invasion and metastasis, and neovascularization. Tumor suppressive roles have also been reported for the receptors, and ligand-dependent versus ligand-independent signaling has emerged as one key mechanism underlying tumor suppressive function as opposed to oncogenic effects. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. Expression profiling in human patient samples bridges this gap and provides valuable clinical relevance to laboratory observations. In addition to analyses performed using privately assembled patient tumor samples, publically available microarray datasets and tissue microarrays linked to clinical data have emerged as tractable tools for addressing the clinical relevance of specific molecules and families of related molecules. This review summarizes the clinical relevance of specific Eph and ephrin molecules in human breast, colorectal, and lung cancers.     

Association of socioeconomic status and receipt of colorectal cancer investigations: a population- based retrospective cohort study

Background

Although the Canadian health care system was designed to ensure equal access, inequities persist. It is not known if inequities exist for receipt of investigations used to screen for colorectal cancer (CRC). We examined the association between socioeconomic status and receipt of colorectal investigation in Ontario.

Methods

People aged 50 to 70 years living in Ontario on Jan. 1, 1997, who did not have a history of CRC, inflammatory bowel disease or colorectal investigation within the previous 5 years were followed until death or Dec. 31, 2001. Receipt of any colorectal investigation between 1997 and 2001 inclusive was determined by means of linked administrative databases. Income was imputed as the mean household income of the person''s census enumeration area. Multivariate analysis was performed to evaluate the relationship between the receipt of any colorectal investigation and income.

Results

Of the study cohort of 1 664 188 people, 21.2% received a colorectal investigation in 1997–2001. Multivariate analysis demonstrated a significant association between receipt of any colorectal investigation and income (p < 0.001); people in the highest-income quintile had higher odds of receiving any colorectal investigation (adjusted odds ratio [OR] 1.38; 95% confidence interval [CI] 1.36–1.40) and of receiving colonoscopy (adjusted OR 1.50; 95% CI 1.48–1.53).

Interpretation

Socioeconomic status is associated with receipt of colorectal investigations in Ontario. Only one-fifth of people in the screening-eligible age group received any colorectal investigation. Further work is needed to determine the reason for this low rate and to explore whether it affects CRC mortality.Colorectal cancer (CRC) is the most common cause of cancer-related death among nonsmokers in North America. In 2004 an estimated 19 200 Canadians will receive a diagnosis of CRC and 8400 will die from the disease.¹ Although the age-standardized incidence and mortality of CRC have been decreasing, the number of new cases is increasing because of the growing size of the elderly population.CRC screening reduces the incidence and disease-specific mortality,^2,3,4,5,6 is cost-effective^7,8 and is endorsed by many professional societies.^{9,10,11,12,13,14,15} In 1994 the Canadian Task Force on the Periodic Health Examination (now the Canadian Task Force on Preventive Health Care) concluded that there was insufficient evidence to support CRC screening in asymptomatic people over the age of 40 years.¹⁶ In the 2001 update of these guidelines⁹ fecal occult blood testing (FOBT) every 1 or 2 years or flexible sigmoidoscopy every 5 years was recommended for screening average-risk people 50 years of age or older; there was judged to be insufficient evidence to support colonoscopy as the initial screening test. Despite these endorsements the use of CRC screening remains suboptimal.^17,18,19The Canadian health care system covers all medically necessary services without user fees. Although equity has been achieved in certain areas,^20,21 low socioeconomic status (SES) is associated with a lower rate of use of cardiovascular procedures^22,23 and screening tests for breast and cervical cancer.^24,25,26 It is unknown whether SES affects the receipt of CRC screening investigations. This study assessed the association of neighbourhood income (a marker of SES) with the receipt of colorectal investigations in people eligible for screening who lived in Ontario.     

Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer.

We investigate the familial risks of cancers of the breast and ovary, using data pooled from three population-based case-control studies of ovarian cancer that were conducted in the United States. We base estimates of the frequency of mutations of BRCA1 (and possibly other genes) on the reported occurrence of breast cancer and ovarian cancer in the mothers and sisters of 922 women with incident ovarian cancer (cases) and in 922 women with no history of ovarian cancer (controls). Segregation analysis and goodness-of-fit testing of genetic models suggest that rare mutations (frequency .0014; 95% confidence interval .0002-.011) account for all the observed aggregation of breast cancer and ovarian cancer in these families. The estimated risk of breast cancer by age 80 years is 73.5% in mutation carriers and 6.8% in noncarriers. The corresponding estimates for ovarian cancer are 27.8% in carriers and 1.8% in noncarriers. For cancer risk in carriers, these estimates are lower than those obtained from families selected for high cancer prevalence. The estimated proportion of all U.S. cancer diagnoses, by age 80 years, that are due to germ-line BRCA1 mutations is 3.0% for breast cancer and 4.4% for ovarian cancer. Aggregation of breast cancer and ovarian cancer was less evident in the families of 169 cases with borderline ovarian cancers than in the families of cases with invasive cancers. Familial aggregation did not differ by the ethnicity of the probands, although the number of non-White and Hispanic cases (N = 99) was sparse.     

The relationship between phosphorylation status of focal adhesion kinases,molecular subtypes,tumour microenvironment and survival in patients with primary operable ductal breast cancer

BackgroundDespite advances in therapies to treat breast cancer, over 100,000 patients die in the UK of this disease per year, highlighting the need to develop effect predictive and prognostic markers for patients with primary operable ductal breast cancer. Therefore, the aim of the present study was to examine the relationship between membranous, cytoplasmic and nuclear expression of focal adhesion kinase (phosphorylated at Y 397, Y 861 and Y 925), molecular subtypes, tumour microenvironment and survival in patients with primary operable ductal breast cancer.MethodsFour hundred and seventy-four patients presenting between 1995 and 1998 with primary operable ductal breast cancer were included in this study. Using tissue microarrays expression of membranous, cytoplasmic and nuclear tumour cell phosphorylation of FAK at Y³⁹⁷, Y⁸⁶¹ and Y⁹²⁵ was assessed, and associations with clinicopathological characteristics, tumour microenvironment and cancer-specific survival (CSS) were examined.ResultsNo significant association was observed for ph-FAK Y⁸⁶¹ with survival at all sites. However, high expression of membranous ph-FAK Y³⁹⁷ was associated with increased tumour grade (P < .001), molecular subtypes (P < .001), increased tumour necrosis (P < .001), high Klintrup–Mäkinen grade (P < .001), increased CD138+ plasma cells (P = .031), endocrine therapy (P = .001) and poor cancer specific survival (P = .040). Similarly, high expression of nuclear ph-FAK Y³⁹⁷ was associated with decreased age (P = .042), increased CD138+ plasma cells (P = .001) and poor cancer specific survival (P = .003). Furthermore, high expression of cytoplasmic ph-FAK Y⁹²⁵ was associated with decreased tumour grade (P < .001), less involved lymph node (P = .020), molecular subtypes (P < .001), decreased tumour necrosis (P < .001), low Klintrup–Mäkinen grade (P < .001), decreased CD4+ T-cells (P = .006), decreased CD138+ plasma cells (P = .034), endocrine therapy (P < .001), chemotherapy (P = .048), and improved cancer specific survival (P = .044). On multivariate analysis, high expression of nuclear ph-FAK Y³⁹⁷ was independently associated with reduced cancer specific survival (P = .017).ConclusionThe results of the present study show that membranous and nuclear ph-FAK Y³⁹⁷ and cytoplasmic ph-FAK Y⁹²⁵ were associated with prognosis in patients with primary operable ductal breast cancer. In addition, high expression of nuclear ph-FAK Y³⁹⁷ was an independent prognostic factor in patients with primary operable ductal breast cancer and could be incorporated into clinical practice.     

Interaction between smoking, GSTM1 deletion and colorectal cancer: results from the GSEC study

Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-μ (GST-μ). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-μ enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (χ²=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype     

Interaction between smoking,GSTM1 deletion and colorectal cancer: results from the GSEC study

Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-μ (GST-μ). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-μ enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (χ²=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype     

Oxidant/antioxidant status in blood of patients with malignant breast tumour and benign breast disease

The aim of this study was to investigate the alterations in lipid peroxidation and antioxidant enzyme defences in the blood of patients with malignant breast tumour and benign breast disease. Forty patients with malignant breast tumour, 20 patients with benign breast disease and also 20 healthy control subjects were recruited for the study. Malondialdehyde levels in plasma and erythrocytes, and the activities of erythrocyte CuZn-superoxide dismutase, catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase were measured. Malondialdehyde levels were higher in patients with both benign breast disease and malignant breast tumour compared with control subjects. The activities of all antioxidant enzymes were higher in patients with malignant breast tumour, while only glutathione peroxidase and CuZn-superoxide dismutase activities were higher in patients with benign breast disease. Except for glucose-6-phosphate dehydrogenase, the antioxidant enzymes studied correlated positively with the malondialdehyde levels in patients with malignant breast tumour. On the other hand, only glucose-6-phosphate dehydrogenase activity was increased by the level of malignancy. The activity increases in erythrocyte antioxidant enzymes may be a compensatory upregulation in response to increased oxidative stress especially in patients with malignant breast tumour.     

Interaction between smoking, GSTM1 deletion and colorectal cancer: results from the GSEC study.

Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-mu (GST-mu). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-mu enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (chi2=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype     

青年与老年非小细胞肺癌患者的术后结果比较

目的:比较青年和老年非小细胞肺癌手术患者,临床特点和术后生存率.方法:我院1997-2002年胸外科肺癌手术患者,根据初诊时的年龄随机选择非小细胞肺癌患者40例作为青年组(≤40岁)和50例作为老年组(≥70岁).对比两组患者的年龄、性别、吸烟史、伴随疾病、病理类型、临床分期、手术方式、术后并发症、5年生存率.结果:青年组的伴随疾病发生率(22.5%)明显低于老年组(50.0%)(P=0.034);青年组的腺癌发生率(52.5%)明显高于老年组(12.0%)(P=0.008),而青年组的鳞癌发生率(32.5%)明显低于老年组(78.0%)(P=0.016);青年组术后并发症发发生率(12.5%)明显低于老年组(32.0%)(P=0.026);青年组5年总生存率(32.2%)明显高于老年组(20.5%)(P=0.041).结论:青年非小细胞肺癌患者以腺癌多见,5年总生存率高于老年组,这可能与老年人伴随疾病和术后并发症较多有关.     

Evaluation of cell-free tumour DNA and RNA in patients with breast cancer and benign breast disease

High levels of DNA and RNA released by apoptotic and necrotic cells circulate in the blood of cancer patients. In the present study we determined the applicability of the quantification of nucleic acids and their genetic alterations as minimally invasive tool for breast cancer screening. The relative concentrations of DNA and RNA were determined in preoperative serum of 102 breast cancer patients, 32 patients with benign breast disease and 53 healthy women. The mean follow-up time of the cancer patients was 6.2 years. Loss of heterozygosity (LOH) at four polymorphic markers (D13S159, D13S280, D13S282 at region 13q31-33 and D10S1765 at PTEN region 10q23.31) was analyzed by PCR-based fluorescence microsatellite analyses using cell-free DNA. The serum levels of DNA (p = 0.016) and RNA (p = 0.001) could differentiate between healthy women and cancer patients, but could not discriminate malignant from benign breast lesions. A significant correlation of serum DNA with RNA levels was observed in all groups (p = 0.018). Increased serum DNA levels (but not RNA levels) in cancer patients were associated with a poorer overall (p = 0.021) and disease-free survival (p = 0.025). The occurrence of LOH at all markers significantly correlated with lymph node status (p = 0.026). In addition, the LOH frequency at D13S280 (p = 0.047) and D13S159 (p = 0.046) associated with overall and disease-free survival, respectively. In conclusion, the quantification of cell-free tumour DNA had diagnostic and prognostic values in breast cancer patients, and DNA loss at the region 13q31-33 may be an indication of lymphatic tumour cell spread.     

Lipid peroxidation and total antioxidant status in patients with breast cancer

Oxidative stress is considered to be involved in the pathophysiology of all cancers. The aim of this study is to examine oxidative stress and antioxidant status in patients with breast cancer by evaluation of the serum levels of total antioxidant capacity (TAC) and lipid peroxidation products as malondialdehyde (MDA) and lipid hydroperoxide and to investigate the relationship between these parameters, oxidative stress and serum lipids and lipoproteins. In our study, serum TAC, MDA, lipid hydroperoxide, HDL-cholesterol, VLDL-cholesterol, LDL-cholesterol, total cholesterol, triacylglycerol (TAG), albumin and uric acid levels of 56-breast cancer patients in different clinical stages and 18 healthy women were determined. Significantly lower-levels of TAC were detected in patients with breast cancer in comparison to controls (2.01 +/- 0.01 mmol/l and 2.07 +/- 0.03 mmol/l, respectively, p < 0.05). Serum MDA levels of the patients were higher compared to the controls (3.64 +/- 0.25 microM and 2.72 +/- 0.22 microM, respectively, p < 0.05). No significant difference between lipid hydroperoxide levels of patients and controls was found (0.33 +/- 0.05 microM and 0.32 +/- 0.01 microM, respectively, p > 0.05). These data show that lower TAC and higher MDA levels i.e. increased oxidative stress may be related to breast cancer.