Ameliorative Effect of Coenzyme Q10 and/or Candesartan on Carboplatin-Induced Nephrotoxicity: Roles of Apoptosis,Transforming Growth Factor-Β1, Nuclear Factor Kappa-B And The Nrf2/HO-1 Pathway

Background: Carboplatin is a drug that is used for treatment of many types of cancer. However, it may produce serious nephrotoxicity. Candesartan is angiotensin II receptor antagonist employed mainly for control of hypertension. Coenzyme Q10 (CoQ10) is a fat-soluble substance which was proven to have potent antioxidant and anti-inflammatory properties. Aim: Our aim was to study the effects of candesartan and/or CoQ10 on carboplatin-induced nephrotoxicity in mice. Methods: Sixty mice were divided into 6 equal groups: Control untreated; carboplatin; carboplatin + candesartan; carboplatin + CoQ10; carboplatin + carboxymethyl cellulose; and carboplatin + candesartan + CoQ10 group. Kidney weight/body weight ratio, blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-D-glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and the urinary albumin excretion rate (UAER) were determined. Renal tissue catalase (CAT), glutathione reductase (GR), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were also determined, along with mitochondrial complex I activity. In addition, portions of the kidney were subjected to histopathological and immunohistochemical examination. Results: Candesartan and/or CoQ10 induced significant improvement of renal and mitochondrial functions with significant increase in tissue CAT, GR, Nrf2 and HO-1 content associated with significant decrease in the kidney weight/body weight ratio, tissue TGF-β1, TNF-α and IL-6 and alleviation of the histopathological and immunohistochemical changes as compared to carboplatin alone group. These effects were more significant in candesartan/CoQ10 combination group compared to either candesartan or CoQ10 alone. Conclusion: Candesartan/CoQ10 combination might represent a beneficial therapeutic modality for amelioration of carboplatin-induced nephrotoxicity.     

Lipid peroxidation, DNA damage and coenzyme Q10 in lung cancer patients--markers for risk assessment?

Objectives: Early diagnosis and prevention is very important for lung cancer patients. Previous studies have emphasized that the level of coenzyme Q10 (CoQ10), present primarily in mitochondria, decreases with age and is low in patients with chronic diseases. Our goal was to find out if there is any relationship between lung cancerand CoQ10 and lipid peroxidation levels. Design and Methods: Blood samples from lung cancer patients were collected. Total and oxide CoQ10 levels, 8-OHdG (product of DNA damage), and malondialdehyde (MDA) levels (lipid peroxidation) were analyzed with high performance liquid chromatography (HPLC). Results: The MDAlevel (P<0.001) and DNA damage rate (8-OHdG) (P<0.001) was higher in cancer patients than in the control group; in contrast, theCoQ10 enzyme level was ignificantly lower (P<0.001). Conclusion: The results suggest t hat the aforementioned parameters can be useful for lung cancer risk assessment.     

Interactions between Oxidative Stress,Lipid Profile and Antioxidants in Breast Cancer: A Case Control Study

Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer.The objective of this study was to determine changes in the levels of malondialdehyde (MDA), nitric oxide (NO),total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, total antioxidant capacity (TAC), glutathioneperoxidase (GSH-Px), and superoxide dismutase (SOD) activities in serum samples of breast cancer patients(n=30) and healthy subjects (n=100). MDA and NO levels were found to be increased in breast cancer patientscompared to the healthy subject group (p<0.05). Total cholesterol and triglycerides were elevated; and HDLcholesterollevel was found to be decreased in the cancer patients as compared to the healthy subjects (p<0.05).Compared to the healthy group, both serum TAC levels (p<0.001) and activity of SOD and GSH-Px (p=0.05) werefound to be decreased in the breast cancer patients as compared to the healthy controls. Considering the datapresented in this study, we suggest that free radicals induce lipid eroxidation and peroxidation of unsaturatedfatty acid with decreased activity of enzymatic antioxidants in breast cancer.     

Assessment of the redox profile and oxidative DNA damage (8-OHdG) in squamous cell carcinoma of head and neck

Background: In developing countries especially in south Asia, there are growing habits of consumption of tobacco and its products in various forms. These are known to generate a strong free radical environment and when the free radicals overwhelm the antioxidant system, they may lead to degeneration of cellular components and mutations. Aim: The aim of this study is to assess the levels of oxidative stress determinants, which may be one of the critical factors in head and neck cancer development. Materials and Methods: This study included 100 consenting SCCHN patients and 90 matched healthy controls and we assessed the total antioxidant capacity (TAC), glutathione (GSH), free radicals (RNS, ROS) and oxidative DNA adduct (8-OHdG). Results: We observed a substantial rise in reactive oxygen species (ROS, ~3.0-fold) and reactive nitrogen species (RNS, ~1.7-fold), together with significant lowering in TAC (~1.2-fold) and GSH (~1.7-fold) was observed. The 8-OHdG levels were also found to be significantly (P < 0.05) higher in patients in comparison to controls. Pearson's correlation between blood ROS and GSH were found to be negatively correlated -0.38 (P < 0.01) and RNS and DNA damage positively correlated 0.44 (P < 0.01). Conclusion: Our present results demonstrate significant Redox imbalance in cancer patients suggesting their paramount importance in the development of SCCHN. The 8-OHdG could be the potential biomarker for evaluating risk of SCCHN. To develop new approaches of SCCHN prevention, there is a need of detailed study and better understanding of the molecular mechanisms underlying oxidative stress and DNA damage.     

Efficacy of coenzyme Q10 for improved tolerability of cancer treatments: a systematic review.

PURPOSE: The aim of this systematic review was to summarize and evaluate the evidence available for oral supplementation with coenzyme Q10 (CoQ10) to improve the tolerability of cancer treatments. MATERIALS AND METHODS: Searches for all published and unpublished controlled trials were carried out on seven databases. Manufacturers of CoQ10 were identified and contacted. Controlled clinical trials of monopreparations of CoQ10 administered orally to cancer patients were included. No language restrictions were imposed. Data were extracted independently by two authors according to predefined criteria. RESULTS: Six studies were included in the review, including three randomized clinical trials and three nonrandomized clinical trials. Patients in five of six studies received anthracyclines. The results suggested that CoQ10 provides some protection against cardiotoxicity or liver toxicity during cancer treatment. However, because of inadequate reporting and analysis, as well as questionable validity of outcome measures, the results are not conclusive. CONCLUSION: Suggestions that CoQ10 might reduce the toxicity of cancer treatments have not been tested by rigorous trials. Further investigations are necessary to determine whether CoQ10 can improve the tolerability of cancer treatments.     

Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats

Reactive oxygen species cause damage to proteins, lipids and DNA. Coenzyme Q10 (CoQ10) is a compound withmitochondrial bioenergetic functions. The reduced form of CoQ10 shows antioxidant activity. In the present study,effects of CoQ10 on development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and mucin-depletedfoci (MDF) in F344 male rats were investigated. To induce ACF and MDF, 6-week old rats were given two weeklysubcutaneous injections of AOM (15 mg/kg body weight) and also received a control diet or experimental dietscontaining CoQ10 (200 or 500 ppm) for 4 weeks, starting one day before the first dose of AOM. At 10 weeks of age,all animals were sacrificed and their colons were evaluated for numbers and sizes of ACF and MDF. Administrationof 200 and 500 ppm CoQ10 resulted in reduction of ACF numbers, to 77% and 68% of the carcinogen control value,respectively. The percentages of ACF consisting of more than 4 crypts in these groups were also significantly lowerthan in the controls. Treatment with 500 ppm CoQ10 furthermore decreased the number of sialomucin-producingACF and MDF per colon to 42% and 38% of the carcinogen control value without CoQ10, respectively. Theseresults suggest that CoQ10 may be an effective chemopreventive agent against colon carcinogenesis.     

Cancer chemotherapy reduces plasma total antioxidant capacity in children with malignancies

The sum of endogenous and food-derived antioxidants provides an estimate of the total antioxidant capacity (TAC) of the extracellular fluids, while corrected TAC (cTAC) is an estimation of the exogenously provided antioxidants. Similar values for TAC and cTAC were observed between cancer free children and children with malignancy at diagnosis. Antineoplastic treatment induced a significant decrease of TAC and cTAC during chemotherapy. Additionally to the dietary factors, this might be attributed to the antineoplastic drugs as shown by the significant increase of ROS after administration of chemotherapeutic agents both in vitro and in vivo. According to our preliminary results TAC and cTAC returned to normal after the end of therapy.     

Aminoflavone induces oxidative DNA damage and reactive oxidative species-mediated apoptosis in breast cancer cells

Aminoflavone (5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methylchromen-4-one; AF; NSC 686288), a novel anticancer candidate agent, is undergoing clinical evaluation. AF induces DNA-protein cross-links (DPCs), Gamma-H2AX phosphorylation, aryl hydrocarbon receptor (AhR) signaling, apoptosis and its own metabolism via cytochrome P4501A1 and 1A2 (CYP1A1/1A2) activation in sensitive estrogen receptor positive (ER+) MCF7 breast cancer cells. Estrogen receptor negative (ER-) breast cancer is typically more aggressive with a poorer prognosis. In this investigation, we evaluated the ability of AF to induce reactive oxygen species (ROS) formation, oxidative DNA damage and apoptosis in ER- MDA-MB-468 breast cancer cells. The antioxidant, N-acetyl-L-cysteine (NAC), attenuated the cytotoxic effects of AF in MDA-MB-468 cells; an effect is also observed in ER+ T47D breast cancer cells. Nonmalignant MCF10A breast epithelial cells were resistant to the cytotoxic effects of AF. AF increased intracellular ROS, an effect blocked by NAC and the CYP1A1/1A2 inhibitor, alpha-Naphthoflavone (alpha-NF). AF induced oxidative DNA damage as evidenced by increased 8-oxo-7,8-dihydroguanine (8-oxodG) levels and DPC formation in these cells. AF caused S-phase arrest corresponding to an increase in p21((waf1/cip1)) protein expression. AF induced caspase 3, 8 and 9 activation, caspase-dependent apoptotic body formation and poly [ADP-ribose] polymerase (PARP) cleavage. Pretreatment with the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp(OMe)-fluoromethylketone inhibited apoptosis and partially inhibited ROS formation and oxidative DNA damage. Pretreatment with NAC attenuated AF-induced apoptotic body formation and caspase 3 activation. These studies suggest AF inhibits the growth of breast cancer cells in part, by inducing ROS production, oxidative DNA damage and apoptosis and has the potential to treat hormone-independent breast cancer.     

Coenzyme Q10 decreases basic fibroblast growth factor (bFGF)-induced angiogenesis by blocking ERK activation

Coenzyme Q10 (CoQ10) is an essential factor of the mitochondrial respiratory chain and has effective antioxidant properties. Therefore, CoQ10 has been used in a variety of clinical applications and used as a nutritional supplement to treat several human diseases. Here, we tested the effects of CoQ10 on angiogenesis stimulated by basic fibroblast growth factor (bFGF). CoQ10 significantly inhibited bFGF-induced angiogenesis in a mouse Matrigel plug and the sprouting of endothelial cells in rat aortic rings. In addition, CoQ10 decreased the ability of tube formation, migration, and invasion in endothelial cells. When CoQ10 was used to inhibit angiogenesis in endothelial cells, the expression of vascular endothelial growth factor (VEGF) and the phosphorylation of ERK were decreased. Taken together, these results indicate that CoQ10 is able to act as an antiangiogenic regulator, and its inhibitory activity is mediated by blocking an ERK-dependent pathway. This study suggests that CoQ10 may be used a therapeutic agent to decrease neovascularization in several diseases, including solid tumors.     

Genetic Variations in VDR could Modulate the Efficacy of Vitamin D3 Supplementation on Inflammatory Markers and Total Antioxidant Capacity among Breast Cancer Women: A Randomized Double Blind Controlled Trial

Background: Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitaminD3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent studies demonstratethe power of vitamin D supplementation to lower inflammation and oxidative stress biomarkers associate with VDRpolymorphism to reduce inflammation. This study was aimed to assess the impact of vitamin D3 supplementation onthe serum concentration of inflammatory markers and antioxidant capacity with regard to VDR polymorphism in theVDR gene in breast cancer women. Methods: A randomized, double-blind, placebo-controlled trial was conducted on 56breast cancer women. Participants were assigned to 2 treatment arms: placebo and vitamin D3 for 2 months intervention.Supplementation group received 50,000 IU of vitamin weekly. Blood samples were collected at baseline and afterthe intervention to measure the 25(OH) D3, TNF-α, TGF- β and TAC. Genotyping was performed for FokI, BsmI, ApaI,and TaqI polymorphism. Results: After eight weeks supplementation, the intervention group showed a significant increasein the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004 and TAC (48.9±13.3 to 63.5±13.3; p= 0.017).Changes in TNF-α, TGF- β1 were not significant. Serum TAC levels of participants with the TT/Tt, Ff genotypes weremore responsive to supplementation. Conclusions: Supplementation with a vitamin D3 increased the TAC in breastcancer women, although it had no effect on inflammatory markers. Serum TAC in the TT/Tt, Ff were more responsive tovitamin D supplement compared with those with the FF/ff and tt genotypes.     

二甲基塞来昔布通过活性氧诱导乳腺癌细胞凋亡

目的:探讨二甲基塞来昔布（2,5-dimethyl celecoxib,DMC）对乳腺癌细胞凋亡的作用。方法:用DMC处理人乳腺癌BT-20和MCF-7细胞,检测细胞生存率、细胞凋亡情况、细胞内ROS的产生;Caspase凋亡通路相关蛋白表达水平;预处理ROS抑制剂NAC、Caspase通路抑制剂Z-VAD-Fmk,检测细胞内Caspase凋亡通路蛋白表达水平。结果:DMC对BT-20和MCF-7细胞呈现浓度及时间依赖性杀伤作用,并可以明显增加细胞的凋亡,且呈现浓度依赖性趋势;DMC可以显著增加BT-20和MCF-7细胞内ROS的产生和凋亡相关蛋白cleaved caspase-7、9的表达水平;另一组实验证明,预处理NAC和Z-VAD-Fmk,可以明显降低cleaved caspase-7、9的表达水平,且抑制剂NAC组的效果大于Z-VAD-Fmk组。结论:DMC通过ROS途径诱导乳腺癌细胞发生凋亡。     

ZnT2-overexpression represses the cytotoxic effects of zinc hyper-accumulation in malignant metallothionein-null T47D breast tumor cells

Human breast tumors accumulate abnormally high levels of zinc (Zn). As a result, numerous studies have implicated Zn hyper-accumulation in the etiology of breast cancer. Zinc accumulation can be cytotoxic, therefore cells have Zn-buffering mechanisms, such as metallothioneins (MT) and vesicular sequestration, which tightly regulate Zn homeostasis. The Zn transporter ZnT2 sequesters Zn into intracellular vesicles and thus can protect cells from Zn cytotoxicity. Herein, we report that malignant breast tumor (T47D) cells do not express MT but have approximately 4-fold greater Zn levels compared with non-malignant breast (MCF-10A) cells. Zinc accumulation coincided with ZnT2 over-expression and increased vesicular Zn pools. In this study, we hypothesized that ZnT2 suppression would eliminate protection from Zn accumulation and result in cytotoxicity in malignant breast tumor cells. Suppression of ZnT2 significantly increased cytoplasmic Zn pools (1.6-fold) as assessed with a Zn-responsive reporter assay containing four metal response elements (4X-MRE) fused to luciferase. Increased cytoplasmic Zn pools activated apoptosis in a caspase-independent manner. We observed significant generation of reactive oxygen species (ROS) (2.3-fold), lysosomal swelling and cathepsin D leakage in ZnT2-attenuated compared with ZnT2-expressing cells. Most importantly, tumor cell viability and tumor formation were significantly decreased (approximately 25%) in ZnT2-attenuated cells compared with ZnT2-expressing cells. Our data indicate that ZnT2 over-expression protects malignant MT-null breast tumor cells from Zn hyper-accumulation by sequestering Zn into intracellular vesicles. Moreover, our results implicate Zn compartmentalizing mechanisms as novel targets for breast cancer therapy.     

Serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 in relation to breast cancer among Hispanic and white, non-Hispanic women in the US Southwest

Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been positively associated with breast cancer, especially among premenopausal women. Hispanic women have lower levels of IGF-1 and IGFBP-3 than non-Hispanic white (NHW) women, although no studies have adequately assessed the relationship among IGF-1, IGFBP-3, and breast cancer in Hispanic women. We investigated the association among IGF-1, IGFBP-3, and breast cancer within a subset of participants (n = 184 cases, 522 controls) of a population-based case–control study of women living in the U.S. Southwest. Serum levels of IGF-1 and IGFBP-3 were measured in fasting blood samples, and associations among IGF-1, IGFBP-3, and breast cancer were calculated using logistic regression, adjusting for age, study center, ethnicity, education, recent hormone exposure, body mass index, parity, total energy expenditure, total calories, and cholesterol. Both IGF-1 and IGFBP-3 were statistically significantly associated with breast cancer overall (highest vs. lowest quartile (Q4 vs. Q1) for IGF-1: odds ratio (OR) = 1.92, 95% confidence interval (CI) = 1.07–3.43); for IGFBP-3: OR = 3.04, 95% CI = 1.63–5.67). Positive associations were observed for both premenopausal breast cancer and postmenopausal breast cancer. IGF-1 was associated with breast cancer in NHW women (Q4 vs. Q1: OR = 2.82, 95% CI = 1.36–5.83), but not in Hispanic women (Q4 vs. Q1: OR = 0.81, 95% CI = 0.29–2.27). IGFBP-3 was associated with breast cancer in both ethnic groups (Q4 vs. Q1 for NHW: OR = 3.32, 95% CI = 1.45–7.60; Q4 vs. Q1 for Hispanics: OR = 2.15, 95% CI = 0.76–6.04). In conclusion, the association between IGF-1 and breast cancer differed by ethnicity, while no ethnic differences were observed in IGFBP-3-associated breast cancer.     

Augmented antioxidant status in Tamoxifen treated postmenopausal women with breast cancer on co-administration with Coenzyme Q10, Niacin and Riboflavin

Background Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide (H₂O₂), hydroxyl radical have been implicated in pathogenesis of various diseases including cancer and metastasis. Tamoxifen (TAM) is a non-steroidal anti-estrogen drug most widely used as an adjuvant hormonal therapy in breast cancer. TAM also has estrogenic activity on liver and endometrium causing severe oxidative stress and hypertriglycerdemia. Coenzyme Q₁₀ (CoQ₁₀), Niacin and Riboflavin are well-known potent antioxidants and protective agents against many diseases including cancer. In this context, this study was undertaken to find if co-administration of CoQ₁₀, Niacin and Riboflavin along with TAM could augment the antioxidant (AO) status in postmenopausal women with breast cancer. Methods The vitamin supplementation with Tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma lipids, lipid peroxides and various circulating enzymatic and non-enzymatic antioxidants were estimated in 78 untreated, sole TAM treated and combinatorial treated group along with 46 age- and sex-matched controls. Results Enhanced oxidative stress as evidenced by increased lipids and lipid peroxides with decreased AO levels in untreated breast cancer patients was observed. Adjuvant TAM-treated group had a limited impact on the increased oxidative stress with decreased AO status. Severe hypertriglycerdemia was observed in TAM-treated group when compared to untreated and control subjects. Combinatorial therapy (CT) of CoQ₁₀, Niacin and Riboflavin along with TAM decreased the oxidative stress and increased the AO status. Conclusion The antioxidant defense system is compromised in breast cancer patients. There is a shift in the oxidant / antioxidant balance in favor of lipid peroxidation (LPO), which could lead to tumour promotion observed in the disease. CT of CoQ₁₀, Niacin and Riboflavin along with TAM significantly increased the AO status, while decreasing lipid and lipid peroxides. The results suggest the necessity of therapeutic co-administration of antioxidants along with conventional drug to such patients. However, due to limited number of cases included in this study, more studies may be required to substantiate the results and arrive at a definitive conclusion, in terms of safety and efficacy of adding an AO therapy in treatment of breast cancer.     

乳腺疾病患者血清中IFN-γ的检测及临床意义

目的:检测乳腺疾病患者及对照组患者血清中IFN-γ的水平,分析其临床意义。方法:收集2014年3月至2015年3月我院转移性乳腺癌患者30例、局部乳腺癌患者35例、乳腺不典型增生患者29例、乳腺纤维瘤患者31例、正常人群30例。应用酶联免疫吸附试验（ELISA法）定量检测IFN-γ在不同组织血清中的水平。比较乳腺癌组与其他各组间血清IFN-γ水平的差异,同时分析乳腺癌组血清中IFN-γ水平与临床病理特征间的关系,探讨检测IFN-γ的临床意义。结果:转移性乳腺癌患者血清中IFN-γ水平明显高于局部乳腺癌组、乳腺不典型增生组、乳腺纤维瘤组及正常人群组,经统计学分析差异均具有统计学意义（F=142.48,P<0.05）。乳腺不典型增生组、乳腺纤维瘤组及正常人群组血清中IFN-γ的组间表达差异无统计学意义(P>0.05)。乳腺癌患者中IFN-γ的表达水平与年龄和肿瘤大小无关(P>0.05),而与TNM分期、组织学分级、淋巴结状态及脉管浸润有关,差异具有统计学意义(P<0.05）。结论:IFN-γ血清水平与乳腺癌发生及侵袭转移相关,可作为一个潜在的乳腺癌血清标志物。     

Decreased plasma zinc levels in metastatic breast cancer

Zinc is an essential component of many metalloenzymes for DNA and proteinsynthesis including RNA and DNA polymerases. It has been shown by several investigators that zinc is accumulated in breast cancer tissues. To investigate a possible relation between plasma zinc levels and tumor load, plasma zinc levels were evaluated in 76 patients with non metastatic breast cancer (no evidence for disease after mastectomy) and in 66 patients with metastatic breast cancer. Zinc concentrations were measured in plasma using an atomic absorption spectrophotometer (normal range 80-150 mcg/dl). In patients with metastatic disease plasma zinc concentrations were in the lower region of the normal range or depressed (arithmetic mean: 84.9 SD 21.6 mcg/dl), whereas patients with non metastatic breast cancer had normal zinc levels (arithmetic mean: 126.0 SD 27.7 mcg/dl). The difference between the two groups was highly significant (p = 0.001, t = -9.742, 140 degrees of freedom). It is concluded, that plasma zinc in breast cancer patients is depressed according to the stage of the disease. Based on experimental data a substitution of zinc cannot be recommended.     

Estimation of individualized probabilities of developing breast cancer for Japanese women

BACKGROUND: Projecting individualized probabilities of developing breast cancer is needed for counseling and chemoprevention for Japanese women, in whom breast cancer incidence has been rapidly increasing. METHODS: We calculated individualized probabilities of developing breast cancer within 10-20 years and until life expectancy for Japanese women by multiplying the relative risk for each risk factor combination by the cumulative risk for the reference group. The risk factors used were age at menarche, age at first delivery, family history of breast cancer, and body mass index (BMI) (in post-menopausal women). The relative risk by menopausal status for each risk factor combination was estimated from a case control study conducted at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), Japan. The cumulative risk of breast cancer for the reference group within 10-20 years and until life expectancy was estimated to divide the corresponding cumulative risk for Japanese women by the weighted average of the relative risk. The weight is an expected proportion of those who have each risk factor combination among the general population. The cumulative risk for Japanese women was estimated using a data file from the Osaka Cancer Registry (OCR). RESULTS: We obtained cumulative risks for any age women within a certain range according to various risk factor combinations by menopausal state. For example, the highest risk group had about a 5 times higher risk probability of developing breast cancer than the general population at initial age 40, within 10-20 years, and until life expectancy. CONCLUSION: The cumulative risk of breast cancer varied according to individuals' risk factors among Japanese women. The availability of concrete individualized risk estimation figures will be of use to health care providers in encouraging Japanese women to seek counseling and to adopt self-control of body weight as a primary preventive measure, as well as to have breast cancer screening.     

Health-related quality of life of breast cancer patients in Iran: pooled analysis using generalized estimating equations

Objective: The aim of current study was to evaluate the changes of health-related quality of life (HRQoL) and its clinical, demographic and socioeconomic determinants during chemotherapy and 4 months follow-up in women with breast cancer using a repeated measures framework. Methods and Materials: A double blind cohort study was performed in 100 breast cancer patients given fluorouracil, doxorubicin and cyclophosphamide (FAC) or docetaxel, doxorubicin, cyclophosphamide (TAC) in south of Iran. HRQoL was assessed at baseline, end of chemotherapy and four months thereafter using the QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer (EORTC). Generalized estimating equations (GEE) was applied for statistical analysis. Results: The mean of age at baseline was 48.5± 10.6. 70% and 14% of patients were married and smokers, respectively, and 20% suffered from another disease besides breast cancer. The results of GEE showed that after control for baseline scores, the HRQoL significantly improved over time. Although, the patients in FAC group had higher scores than the TAC group, the differences also diminished over time. Smoking, marital status and having child affected some scales of HRQoL. None of other variables were significantly related to HRQoL. Conclusion: Although patients in TAC groups had lower level of HRQoL over 8 months follow up, they experienced faster improvement than the FAC group. This implies that in long-term, improvements in TAC group are higher than FAC. Having children was positively correlated with HRQoL. Generally, there were no demographic and socio-economic differences in HRQoL in these patients between the chemotherapeutic regimens.     

Risk factors for breast cancer at young ages in twins: an international population-based study

BACKGROUND: Breast cancer etiology in women may relate to exposures early in life as well as in adulthood, but it has been difficult to gain information on childhood variables, and evidence on their effects is very limited. Comparison of risk factor levels between affected probands and unaffected twins in twin pairs can provide a unique method to investigate risk factors that act in early life. METHODS: We conducted four population-based case-control studies of breast cancer risk in twins in Denmark, England and Wales, Finland, and Sweden and pooled the data from these studies. The case patients were 400 women with incident breast cancer before the age of 50 years, and the control subjects were their twin sisters who had not had breast cancer by that time. Data on risk factors (e.g., demographic and anthropomorphic variables, reproductive history, and family history) were collected by interview and by a mailed questionnaire and were analyzed by calculating matched odds ratios [ORs]. All statistical tests were two-sided. RESULTS: The risk of breast cancer was increased for women who were less obese (OR = 1.44, 95% confidence interval [CI] = 1.08 to 1.91) or taller (OR = 1.27, 95% CI = 0.95 to 1.70) than their co-twin at age 10 years, for women who developed breasts earlier than their co-twin (OR = 1.53, 95% CI = 1.14 to 2.06), and for women who had a smaller waist-to-hip ratio at age 20 years than their co-twin (OR = 1.79, 95% CI = 1.00 to 3.21). Analysis according to family history of breast cancer showed that the associations of childhood height and weight with risk of breast cancer were only apparent in women without a family history of breast cancer. CONCLUSIONS: Childhood growth before puberty may affect the risk of premenopausal breast cancer, at least in women without a family history of breast cancer. The distribution of body fat in young adulthood may also be related to breast cancer risk.