Estrogen receptor-α polymorphism in a Taiwanese clinical breast cancer population: a case–control study

Introduction

Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated.

Design

To examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses.

Conclusions

Our study design improves the potential for detecting gene–environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case–control sets and enhanced our ability to detect radiation–genotype interactions.     

Breastfeeding reduces breast cancer risk: a case–control study in Tunisia

In this report, we examined the relationship between mother’s breastfeeding history and her risk of breast cancer, in a case–control study in Tunisia between 2006 and 2009. About 400 breast cancer cases and 400 controls were included. Cases and controls were interviewed using a standardized structured questionnaire to obtain information on breastfeeding and other risk factors. Mean duration of breastfeeding per child was significantly associated with a reduced risk of breast cancer for women who breastfed for >24 months per child. The OR was 0.46 (95% CI, 0.28–0.76) when compared those who breastfed for <6 months. The test for trend was significant (p = 0.01). A significantly reduced risk of breast cancer was found for those whose lifetime duration of breastfeeding was 73–108 months (OR = 0.65, 95% CI, 0.36–1.18) and for those who breastfed for ≥109 months (OR = 0.42, 95% CI, 0.20–0.84). Stratification by menopausal status showed a reduced risk of breast cancer associated with a longer duration of breastfeeding for both pre- and postmenopausal women. The risk reduction was more consistent for lifetime duration of breastfeeding, the test for trend being significant for both pre- (p = 0.03) and postmenopausal (p = 0.01) women. These results support an inverse association between breastfeeding and breast cancer risk.     

Gamma-ray-induced mutagen sensitivity and risk of sporadic breast cancer in young women: a case–control study

Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of breast cancer. In this case–control study of 515 young women (≤55 years) with newly diagnosed sporadic breast cancer and 402 cancer-free controls, we examined the radiosensitivity as measured by the frequency of chromatid breaks induced by gamma-radiation exposure in the G2 phase of phytohemagglutinin-stimulated and short-term cultured fresh lymphocytes. We found that the average chromatid breaks per cell from 50 well-spread metaphases were statistically significantly higher in 403 non-Hispanic White breast cancer patients (0.52 ± 0.22) than that in 281 non-Hispanic White controls (0.44 ± 0.16) (P value < 0.001), and in 60 Mexican American breast cancer patients (0.52 ± 0.19) than that in 65 Mexican American controls (0.44 ± 0.16) (P value = 0.021), but the difference was not significant in African Americans (52 cases [0.45 ± 0.16] versus 56 controls [0.47 ± 0.16], P = 0.651). The frequency of chromatid breaks per cell above the median of control subjects was associated with two-fold increased risk for breast cancer in non-Hispanic Whites and Mexican Americans. A dose–response relationship was evident between radiosensitivity and risk for breast cancer (P _trend < 0.001) in these two ethnic groups. We concluded that gamma-ray-induced mutagen sensitivity may play a role in susceptibility to breast cancer in young non-Hispanic White and Mexican American women.     

Breast cancer risk in women with a primary ovarian cancer—a case–control study

Register-based studies show that women with ovarian cancer are at increased risk of developing breast cancer. Primary suggested explanations are heredity factors and a common hormonal aetiology. However, clinical surveillance that is provided for cancer patients during, and after, treatment of their primary malignancies together with possible mistakes in the registering procedures could affect the risk estimates. In order to examine these factors in women registered with ovarian cancer who develop subsequent breast cancer, a case–control study was performed. Using a regional Swedish cancer registry including 5060 women registered with ovarian cancer, 89 cases of breast cancer were found. After corrections for discrepancies in the registered and recorded information, 75 cases remained, of which 72 cases were included in the study. Information concerning possible risk factors were extracted from hospital records and compared with 177 matched controls. Suggested risk factors such as parity (relative risk (RR)=1.41), late age at menopause (52–61 years; RR=1.61) and heredity for breast and/or ovarian cancer (RR=1.50) were all connected with a non-significant increased risk of subsequent breast cancer. In all, 43% of the breast cancer cases were revealed without preceding symptoms at clinical follow-up, indicating that increased clinical surveillance is a factor of importance when explaining the increased risk. The fact that only 75 (missing records included) out of the 89 registered breast cancer cases could be linked to the preceding ovarian cancer indicates that the actual risk of developing breast cancer is smaller than previously described. The clinical implications from these findings could be that, beside general screening programmes and health controls offered to women in cancer-prone families, additional mammography examinations based on the assumption of an increased risk of breast cancer are not warranted in ovarian cancer patients.     

MUTYH gene variants and breast cancer in a Dutch case–control study

The MUTYH gene is involved in base excision repair. MUTYH mutations predispose to recessively inherited colorectal polyposis and cancer. Here, we evaluate an association with breast cancer (BC), following up our previous finding of an elevated BC frequency among Dutch bi-allelic MUTYH mutation carriers. A case–control study was performed comparing 1,469 incident BC patients (ORIGO cohort), 471 individuals displaying features suggesting a genetic predisposition for BC, but without a detectable BRCA1 or BRCA2 mutation (BRCAx cohort), and 1,666 controls. First, for 303 consecutive patients diagnosed before age 55 years and/or with multiple primary breast tumors, the MUTYH coding region and flanking introns were sequenced. The remaining subjects were genotyped for five coding variants, p.Tyr179Cys, p.Arg309Cys, p.Gly396Asp, p.Pro405Leu, and p.Ser515Phe, and four tagging SNPs, c.37-2487G>T, p.Val22Met, c.504+35G>A, and p.Gln338His. No bi-allelic pathogenic MUTYH mutations were identified. The pathogenic variant p.Gly396Asp and the variant of uncertain significance p.Arg309Cys occurred twice as frequently in BRCAx subjects as compared to incident BC patients and controls (p=0.13 and p=0.15, respectively). The likely benign variant p.Val22Met occurred less frequently in patients from the incident BC (p=0.03) and BRCAx groups (p=0.11), respectively, as compared to the controls. Minor allele genotypes of several MUTYH variants showed trends towards association with lobular BC histology. This extensive case–control study could not confirm previously reported associations of MUTYH variants with BC, although it was too small to exclude subtle effects on BC susceptibility.     

Serum organochlorines and breast cancer risk in Japanese women: a case–control study

Objective  Most epidemiological studies of the association between breast cancer risk and exposure to organochlorine pesticides or polychlorinated biphenyls (PCBs), which are suspected endocrine disrupters and potential risk factors for human breast cancer, have been conducted in western countries, and the majority of results have been null and the rest inconsistent. Here, we examined these associations in Japanese women in the largest study in Asian women to date. Methods  The study was a matched case–control study of breast cancer with 403 eligible matched pairs from May 2001 to September 2005 at four hospitals in Nagano Prefecture, Japan. Measurements  Serum samples were measured for PCBs and nine pesticide-related organochlorines, including dichlorodiphenyltrichloroethane (DDT). Odds ratios of breast cancer or its hormone-receptor-defined subtypes according to serum organochlorines were calculated. Results  No increase in the risk of breast cancer was seen among women with higher serum concentrations of any organochlorine: o,p′-DDT, p,p′-DDT, p,p′-dichlorodiphenyldichloroethylene, hexachlorobenzene, β-hexachlorocyclohexane, trans-nonachlor, cis-nonachlor, oxychlordane, mirex, or PCBs. Rather, higher serum levels of cis-nonachlor, mirex, or total PCBs were associated with a decreased risk of breast cancer Conclusions  Overall, these results suggest that breast cancer risk in Japan, a low-incidence country, is similar to that in western countries in terms of organochlorine exposure.     

Treatment outcomes for male breast cancer: a single-centre retrospective case–control study

Background

Male breast cancer (bc) is a rare disease, and the availability of information on treatment outcomes is limited compared with that for female bc. The objective of the present study was to compare disease-free (dfs) and overall survival (os) for men compared with women having early-stage bc.

Methods

This retrospective case–control study compared men and women treated for stage 0–iiib bc at a single institution between 1981 and 2009. Matching was based on age at diagnosis, year of diagnosis, and stage. Treatment, recurrence, and survival data were collected. Kaplan–Meier analysis was used to calculate os and dfs.

Results

For the 144 eligible patients (72 men, 72 women), median age at diagnosis was 66.5 years. Treatments included mastectomy (72 men, 38 women), radiation (29 men, 44 women), chemotherapy (23 men, 20 women), and endocrine therapy (57 men, 57 women). Mean dfs was 127 months for women compared with 93 months for men (p = 0.62). Mean os was 117 months for women compared with 124 months for men (p = 0.35). In multivariate analysis, the only parameter that affected both dfs and os was stage at diagnosis.

Conclusions

This case–control study is one of the largest to report treatment outcomes in early-stage male bc patients treated in a non-trial setting. Male patients received systemic therapy that was comparable to that received by their female counterparts, and they had similar os and dfs. These results add to current evidence from population studies that male sex is not a poor prognostic factor in early-stage breast cancer.     

Serum organochlorines and breast cancer: a case–control study among African-American women

This population-based case–control study of African-American women (355 breast cancer case patients, 327 controls) examined the association between breast cancer and circulating levels of PCBs and dichlorodiphenyldichloroethene (DDE), a metabolite of DDT. Case patients were diagnosed with invasive breast carcinoma and interviewed between June 1995 and July 1998, and control subjects were identified by random digit dialing methods. Serum levels of DDE and total PCBs were adjusted for total lipid content. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable unconditional logistic regression methods. Effect modification by tumor receptor status and cancer treatment was investigated. Breast cancer risk was not associated with increasing quintiles of lipid-adjusted PCBs or DDE (highest versus lowest quintile adjusted for age, body mass index (BMI) and breastfeeding for DDE: OR = 1.02, 95% CI = (0.61, 1.72), p-trend = 0.74; for PCBs: OR = 1.01, 95% CI = (0.63, 1.63), p-trend = 0.56). Risk did not differ by strata of BMI, breastfeeding, parity, menopausal status or tumor receptor status. This study, the largest study of African-American women to date, does not support a role of DDE and total PCBs in breast cancer risk at the levels measured.     

Features of cancer in teenagers and young adults in primary care: a population-based nested case–control study

Background:

Teenagers and young adults (TYA, 15–24 years) diagnosed with cancer report repeated visits to primary care before referral. We investigated associations of symptoms and consultation frequency in primary care with TYA cancers.

Methods:

Population-based, case–control study was carried out using data from the Clinical Practice Research Datalink (CPRD). A total of 1064 TYA diagnosed with cancer were matched to 13 206 controls. Symptoms independently associated with specific cancers were identified. Likelihood ratios (LRs) and positive predictive values (PPVs) were calculated.

Results:

In the 3 months before diagnosis, 397 (42.9%) cases consulted ⩾4 times vs 593(11.5%) controls (odds ratio (OR): 12.1; 95% CI: 9.7, 15.1), yielding a PPV for any cancer of 0.018%. The LR of lymphoma with a head/neck mass was 434 (95% CI: 60, 3158), with a PPV of 0.5%. Corresponding figures in other cancers included – LR of leukaemia with lymphadenopathy (any site): 29 (95% CI: 8, 112), PPV 0.015% LR of CNS tumour with seizure: 56 (95% CI: 19, 163), PPV 0.024% and LR of sarcoma with lump/mass/swelling: 79 (95% CI: 24, 264), PPV 0.042%.

Conclusion:

Teenagers and young adults with cancer consulted more frequently than controls in the 3 months before diagnosis. Primary care features of cancer match secondary care reports, but were of very low risk; nonetheless, some features increased the likelihood of cancer substantially and should be taken seriously when assessing TYA.     

History of benign breast disease and risk of breast cancer among women in China: a case–control study

Background  Data from the Shanghai Breast Cancer Study were analyzed to evaluate the relationship between benign breast disease (BBD) and breast cancer among Chinese women with a self-report of physician-diagnosed BBD. Methods  Study participants consisted of 3,452 breast cancer cases and 3,474 population controls recruited by the Shanghai Breast Cancer Study. In-person interviews were conducted to collect information on demographics and suspected risk factors for breast cancer, including a detailed history of BBD. Unconditional logistic regression was used to derive adjusted odds ratios (OR_adj) and 95% confidence intervals (CI) for the association between self-reported BBD and breast cancer. Results  Women with breast cancer were significantly more likely to have a self-reported history of BBD including lobular proliferation (OR_adj = 1.6; 95% CI 1.4–1.8), fibroadenoma (OR_adj = 1.9; 95% CI 1.6–2.3), and other BBD (OR_adj = 1.6; 95% CI 1.3–2.1). Breast cancer risk was lower for surgically treated fibroadenoma as compared to non-surgically treated and higher for other BBDs that were surgically treated versus non-surgically treated. Conclusions  Our results suggest that personal history of BBD is associated with an increased risk of future breast cancer among women in China. Surgical intervention for fibroadenoma may reduce the risk.     

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case–control study

Purpose

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer.

Methods

Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical–pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical–pathologic features was assessed using Cox proportional hazard models.

Results

Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages.

Conclusion

Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

     

Oestrogen receptor α gene haplotype and postmenopausal breast cancer risk: a case control study

Introduction

Oestrogen receptor α, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor α gene (ESR1) are associated with breast cancer risk.

Methods

We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TA _n , 1514 cases and 1514 controls; c.454-397C → T, 1557 cases and 1512 controls; c.454-351A → G, 1556 cases and 1512 controls; c.729C → T, 1562 cases and 1513 controls; c.975C → G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data.

Results

There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A → G or c.454-397C → T and c.975C → G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A → G and c.975C → G haplotype entailed an OR of 1.19 (95% CI 1.06–1.33) and two copies with an OR of 1.42 (95% CI 1.15–1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C → T and c.975C → G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant.

Conclusion

We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.     

Breast cancer screening case–control study design: impact on breast cancer mortality

BackgroundRecent case–control studies on the effectiveness of population-based breast cancer screening show differences in the magnitude of breast cancer mortality reduction. We investigated the role played by aspects of the case–control study design on these differences, e.g. the definition of cases and exposure to screening.Material and methodsWe investigated six case–control studies conducted in East Anglia (UK), Wales, Iceland, central and northern Italy, South Australia and The Netherlands.ResultsThe breast cancer mortality reduction in the different case–control studies ranged from 38% to 70% in the screened versus the nonscreened women. We identified differences in design, e.g. the inclusion or exclusion of the first years of screening, and the correction factor for self-selection bias.ConclusionsOverall, the design of the case–control studies was similar. The differences in the magnitude of breast cancer mortality reductions are therefore unlikely to be caused by variations in the design of the case–control studies. These differences must be due to other factors, like the organisation of the service screening programme and the attendance rate. The reduction in breast cancer mortality estimated in these case–control studies indicates that the impact of current mammographic screening is at least consistent with the effect reported by the former randomised screening trials.     

Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk in Chinese population: a meta-analysis of 22 case–control studies

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk in the Chinese population has been widely reported, but results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified through search of databases including Medline, PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China National Knowledge Infrastructure (CNKI, Chinese), and Wangfang Database (Chinese). The association between the MTHFR polymorphism and breast cancer risk was conducted using odds ratios (ORs) and 95 % confidence intervals (95 % CIs). Finally, a total of 22 studies with 6,103 cases and 7,913 controls were included in our meta-analysis: 13 studies with 3,273 cases and 4,419 controls for C677T polymorphism and 9 studies with 2,830 cases and 3,494 controls for A1298C polymorphism. With regard to C677T polymorphism, significant association was found with breast cancer risk under three models (T vs. C: OR?=?1.12, 95 % CI?=?1.02–1.23, P?=?0.015; TT vs. CC: OR?=?1.35, 95 % CI?=?1.10–1.67, P?=?0.005; TT vs. CC/CT: OR?=?1.37, 95 % CI?=?1.11–1.70, P?=?0.004). There was no significant association found between A1298C polymorphism and breast cancer risk under all genetic models (C vs. A: OR?=?0.96, 95 % CI?=?0.89–1.03, P?=?0.268; CC vs. AA: OR?=?0.98, 95 % CI?=?0.77–1.26, P?=?0.899; AC vs. AA: OR?=?0.95, 95 % CI?=?0.88–1.02, P?=?0.174; CC vs. AC/AA: OR?=?1.00, 95 % CI?=?0.78–1.28, P?=?0.996, CC/AC vs. AA: OR?=?0.96, 95 % CI?=?0.89–1.02, P?=?0.196). In summary, during this meta-analysis, we found that MTHFR C677T polymorphism was significantly associated with breast cancer risk in the Chinese population. Meanwhile, MTHFR A1298C polymorphism was not associated with breast cancer risk in the Chinese population.     

Plasma matrix metalloproteinases and postmenopausal breast cancer risk: a nested case–control study in the Multiethnic Cohort study

The survival of malignant breast cells depends upon the remodeling of the extracellular matrix, including complex interactions with matrix metalloproteinases (MMPs). It has been hypothesized that circulating MMPs may serve as early indicators of breast cancer development in hospital-based case–control studies. A nested case–control study of the association of pre-diagnostic plasma levels of MMPs with the subsequent risk of postmenopausal breast cancer was conducted within the Multiethnic Cohort. During the follow-up period, 713 women with incident invasive breast cancer were identified and individually (1:1) matched to controls. Four types of MMPs (1, 2, 3, and 7) were analyzed by microsphere immunofluorescence assay. Mean plasma levels of MMPs did not differ significantly between cases and controls; nor were there differences in breast cancer risk by MMP level. No difference in the risk of breast cancer by plasma level of the MMPs was found within strata of age, or ethnicity, although MMP-1 levels were positively associated with breast cancer risk in obese women and women by hormone replacement medications (P values for interaction <0.05). Few significant differences in risk by levels of the MMPs were found by any of the clinical variables. Circulating MMPs were not associated with postmenopausal breast cancer risk.     

Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer

Background:

Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population.

Methods:

Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case–control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer.

Results:

The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9–8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12–3.8) years before clinical diagnosis.

Conclusion:

Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.     

A comparison of hormonal profiles between breast cancer and benign breast disease: a case–control study

BackgroundBenign breast disease (BBD), particularly proliferative BBD, is an established breast cancer risk factor. However, there has been no systematic attempt to compare the hormonal profiles of the two conditions. In a case–control investigation in Athens, Greece, we compared levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1), as well as their principal binding proteins, between breast cancer patients, women with BBD by histological type (proliferative and nonproliferative) and women with no breast pathology.Patients and methodsWe studied 466 women with incident breast cancer, 704 women with BBD and 244 healthy women. We used multiple regression to compare log-transformed serum hormone levels of breast cancer patients with those of healthy women and women with BBD by histological type (proliferative and nonproliferative BBD).ResultsThe hormonal profile of breast cancer in our study was in line with the generally accepted hormonal profile of this disease, as reported from large cohort studies. Compared with healthy women, breast cancer patients tended to have higher levels of steroid hormones. The evidence was strong for estrone (difference 21.5%, P < 0.001), weaker for testosterone (difference 15.8%, P = 0.07) and weaker still for estradiol (difference 12.0%, P = 0.18). Also compared with healthy women, breast cancer patients had barely higher levels of IGF-1 (difference 2.0%, P = 0.51), but had significantly lower levels of IGF binding protein 3 (IGFBP-3) (difference -6.7%, P = 0.001). Compared with women with BBD, breast cancer patients had nonstatistically significantly lower levels of steroid hormones, but they had higher levels of IGF-1 [difference 5.5%, 95% confidence interval (CI) 0.7% to 10.6%] and lower levels of IGFBP-3 (difference -3.7%, 95% CI -6.7% to -0.7%). Differences were more pronounced when breast cancer patients were contrasted to women with proliferative BBD.ConclusionsOur findings suggest that high levels of IGF-1 may be an important factor toward the evolution of BBD to breast cancer.     

Flavonoid intake and liver cancer: a case–control study in Greece

In the context of a case–control study undertaken in Greece, we examined the role of six flavonoid classes in the etiology of hepatocellular carcinoma (HCC), by viral status, and of cholangiocarcinoma (CAC). Data and blood samples were collected between 1995 and 1998. Information about dietary intakes and covariates, including chronic infection with hepatitis B (HBV) and C (HCV) virus, were available for 250 HBV and/or HCV positive HCC cases, 83 HBV and HCV negative HCC cases, six CAC cases, and 360 hospital controls. In logistic regression models including gender, age, education, tobacco smoking, and total energy intake, there were no distinct patterns with respect to either HCC virus positive and HCC virus negative in relation to total flavonoids or any class of flavonoids, with the exception of flavones. Flavone intake, mostly derived from spinach and peppers, was inversely associated with both virus positive (P-trend, 0.049) and virus negative (P-trend, 0.084) HCC. There was also a suggestion of an inverse association of CAC with flavan-3-ols, anthocyanidins, and total flavonoids which, however, has to be taken with due caution on account of the small number of cases of this rare tumor. We conclude that flavones may be inversely associated with HCC risk, irrespective of its dominant etiology (viral or non viral).     

Dietary patterns and the risk of postmenopausal breast cancer in a German case–control study

Objective  

Dietary patterns have been inconsistently associated with breast cancer risk. We assessed dietary patterns in association with postmenopausal breast cancer risk using an exploratory approach.     

A case–control study of non-alcoholic fatty liver disease in breast cancer

Background Patients with breast cancer sometimes present with increased liver enzymes during follow-up period that may be consistent with hepatic steatosis. This effect known as non-alcoholic fatty liver disease may be associated with the malignancy itself, drugs or some other well-known risk factors that may induce steatosis. We studied the influences of primary disease and treatment on steatosis in patients with breast cancer. Materials and methods There were four groups of patients in our study. Group 1: 40 newly diagnosed, previously untreated breast cancer; Group 2: 45 cases of breast cancer treated with systemic therapy; Group 3: 40 cases of ovarian cancer; Group 4: 40 healthy women. Hepatic steatosis was evaluated by sonography by two radiologist, independently. We also evaluated major risk factors, biochemical findings, and influences of treatment on hepatic steatosis. Results We detected steatosis in 63%, 72%, 77%, and 48% of patients in groups 1, 2, 3, and 4, respectively. There was a statistically significant difference only between groups 3 and 4 (P = 0.045). However, grade 2 and 3 steatosis were more frequent in breast cancer patients (group 1 and 2), compared with mild steatosis in ovarian cancer patients and healthy women. Although a good correlation was found between tamoxifen use and chemotherapy on development of non-alcoholic fatty liver disease, no association of hepatic steatosis with transaminase levels was found, which might be of help for earlier detection of steatosis. AST/ALT ratio was found to have no impact on the rate of hepatic steatosis, contrary to the literature. Conclusion Hepatic steatosis, excluding patients with grade 1 steatosis, which may be a normal variant, were more readily detected in patients with breast cancer. This effect was aggravated by use of tamoxifen, but not the chemotherapy. Non-alcoholic fatty liver disease in patients with breast cancer may be associated with the primary tumor itself or some well-known risk factors such as obesity, hyperlipidemia, and diabetes mellitus, which needs to be explored.