UMLS:C0006142 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0006142 (breast cancer)
160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of the epidermal growth factor receptor (egfr) gene in human cancer is not yet fully understood. Recent data on a polymorphic CA repeat located at the 5'-regulatory sequence in intron 1 of the egfr gene [egfr CA simple sequence repeat (SSR) I] point to a possible inheritance of cancer risk associated with the egfr gene. Furthermore, we have detected frequent allelic imbalances restricted to the egfr CA SSR I in breast cancer tissue and nontumorous breast tissue adjacent to invasive and in situ breast cancer representing amplifications. Therefore, we conducted a population-based case-control study to assess the relationship between the egfr polymorphism and breast cancer risk. Cases with a first primary breast cancer by age 50 years and age-matched population controls provided information on known and suspected risk factors. The allelic length of the egfr CA SSR was determined in 616 cases and 1072 population-sampled controls. Genotypes were categorized for analysis by allele length. Multivariate logistic regression was used to compare genotype distributions, accounting for other risk factors, and to investigate gene-environment interactions. We found a modifying effect, albeit no main effect, of the allelic length of the egfr polymorphism on breast cancer risk. The presence of two long alleles (>/==" BORDER="0">19 CA) was associated with a significantly elevated odds ratio (OR) of 10.4 [95% confidence interval (CI), 1.85-58.70] among women with a first-degree family history of breast cancer (P = 0.015 for interaction). The risk increase associated with high red meat consumption (OR, 10.68; 95% CI, 1.57-72.58) and the protective effect of high vegetable intake (OR, 0.07; 95% CI, 0.004-1.07) was also most pronounced among carriers of two long alleles (>/==" BORDER="0">19 CA). The length of the egfr CA SSR may increase the risk for familial breast cancers, and its effect could be modulated by dietary factors.
...
PMID:Modification of breast cancer risk in young women by a polymorphic sequence in the egfr gene. 1472 99

Cyclooxygenase type-2 (COX-2) is overexpressed in malignant tumours including breast cancers, though the mechanism of upregulation is unclear. This study aimed to determine COX-2 expression in ductal carcinoma in situ (DCIS) in comparison to invasive breast cancer (IBC) and normal breast, and also to investigate the relationship of COX-2 expression with HER-2 expression, oestrogen receptor (ER), tumour grade and cellular proliferation (Ki67) in DCIS. Cyclooxygenase type-2, HER-2, ER and Ki67 expression were determined by immunohistochemistry on paraffin tissue sections of DCIS (n=187), IBC (n=65) and normal breast reduction tissue (n=60). Cyclooxygenase type-2 expression in DCIS (67%, P<0.001) and IBC (63%, P<0.001) was significantly greater than in normal breast (23%). There was no difference in COX-2 expression level between DCIS and IBC (P=0.87) or between normal breast from reduction mammoplasty tissue and normal breast ducts around DCIS (22%, P=0.29). In DCIS, COX-2 expression was associated with higher cellular proliferation rates (P<0.0001), nuclear grade (P=0.003), with ER negativity (P=0.003) and with HER-2 positivity (P<0.0001). Cyclooxygenase type-2 expression is upregulated in in situ breast cancer and is associated with surrogate markers of an aggressive DCIS phenotype including nonoestrogen-regulated signalling pathways. Cyclooxygenase type-2 inhibition may potentially prevent the development of ER-positive and ER-negative breast cancers.
...
PMID:COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ. 1473 88

Socio-economic gradients are known to exist in cancer but we want to focus on the university-educated population and specifically on physicians to find out whether their special educational background on cancer causation helps them to avoid cancers. The analysis was based on the latest update of the Swedish Family-Cancer Database, in which the educational level was obtained from the national census of 1970 for those aged 30 years or older and the follow-up for cancer was extended up to year 2000. We determined standardized incidence ratios (SIRs), adjusted for several variables, for cancer among men and women in four educated groups and compared them with those with less than 9 years of education. Total cancer risks did not differ much, but at individual sites, the university-educated population showed consistent, increasing or decreasing trends. The educated group showed high SIRs for melanoma and skin cancer and for female breast cancer. At all these sites, SIRs for in situ tumours exceeded those for invasive tumours; the highest SIR was 4.81 for male MD, PhDs for in situ melanoma. SIR for in situ breast cancer for female physicians was 1.95. SIR for non-Hodgkin's lymphoma for male MD, PhDs was 2.20 but their risk of stomach cancer was only 0.26. Tobacco-related cancers were decreased among the educated group. Cancer risks for physicians were not different from those of their academic colleagues. Some of the increased risks were probably due to lead-time bias, caused by early diagnosis.
...
PMID:University and medical education and the risk of cancer in Sweden. 1516 19

Sweden was the first country to establish a nationwide breast cancer screening service. We used the Swedish Family-Cancer Database to evaluate the risk of invasive carcinoma after in situ carcinoma of the breast. Risk estimates for contralateral and ipsilateral invasive malignancies following age and histology specific in situ breast carcinomas were calculated using Poisson's regression analysis. The agreement between concordant and discordant morphologies of invasive and in situ breast cancer was measured using the kappa statistic. Women with in situ breast cancer showed a relative risk of 2.03 for contralateral and 3.94 for ipsilateral invasive breast cancer. The risk was higher for in situ carcinomas diagnosed before the age of 50 years and after lobular in situ breast cancers. A comparison of the risks during the past decades suggested that the risk of ipsilateral breast cancer has increased in Sweden but that of contralateral breast cancer has remained unchanged. In situ and the subsequent invasive breast cancers did not seem to share their morphologies.
...
PMID:Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening. 1557 Mar 9

Exposure to light at night suppresses melatonin production, and night-shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. However, the association between circulating melatonin levels and breast cancer risk is unclear. In a prospective case-control study nested within the Nurses' Health Study II cohort, we measured the concentration of the major melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in the first morning urine of 147 women with invasive breast cancer and 291 matched control subjects. In logistic regression models, the relative risk (reported as the odds ratio [OR]) of invasive breast cancer for women in the highest quartile of urinary aMT6s compared with those in the lowest was 0.59 (95% confidence interval [CI] = 0.36 to 0.97). This association was essentially unchanged after adjustment for breast cancer risk factors or plasma sex hormone levels but was slightly weakened when the analysis included 43 case patients with in situ breast cancer and their 85 matched control subjects (OR = 0.70, 95% CI = 0.47 to 1.06). The exclusion of women who had a history of night-shift work left our findings largely unchanged. These prospective data support the hypothesis that higher melatonin levels, as measured in first morning urine, are associated with a lower risk of breast cancer.
...
PMID:Urinary melatonin levels and breast cancer risk. 1603 Mar 7

Second malignancies in women diagnosed with thyroid cancer are of concern given the young average age at diagnosis and excellent survival. Data from the California Cancer Registry were used to evaluate the risk of second primary cancers among a retrospective population-based cohort of 10,932 women diagnosed with papillary thyroid cancer between 1988 and 1999. Follow-up was calculated from 2 months until the diagnosis of a second primary cancer, death, loss to follow-up, or December 31, 1999, whichever occurred first. Standardized incidence ratios, based on age-specific cancer incidence rates for California women, were calculated. During a total of 50,938 person-years of follow-up (mean: 4.7 years), 279 women developed a second primary cancer. The incidence of invasive breast cancer was not elevated compared with California women overall (standardized incidence ratio (SIR) = 0.9, 95% confidence interval (CI): 0.7, 1.1) or when stratified by age, race/ethnicity, follow-up, or radiation treatment. An excess of in situ breast cancer (SIR = 1.6, 95% CI: 1.0, 2.4), kidney cancer (SIR = 3.9, 95% CI: 2.2, 6.3), and melanoma (SIR = 2.1, 95% CI: 1.3, 3.2) limited to the first 5 years after diagnosis was observed. Women with papillary thyroid cancer are at increased risk of in situ, but not invasive, breast cancer, kidney cancer, and melanoma.
...
PMID:Risk of second primary malignancies in women with papillary thyroid cancer. 1713 99

Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses' Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69-1.39; IGFBP-1, 0.95, 95% CI, 0.63-1.41; IGFBP-3, 1.10, 95% CI, 0.78-1.54; GH, 1.09, 95% CI, 0.82-1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.
...
PMID:Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II. 1672 84

Only little information on the primary molecularbiological events involved in early breast is available. In particular, the definition of postulated precursor lesions of invasive breast cancer, such as ductal hyperplasia or ductal carcinoma in situ, is under an intense, controversial discussion in terms of pathogenesis and tumor biology. The most recent research on biological regulation mechanisms and genetic alterations in morphologically normally appearing breast tissue give rise for a reinterpretation for the most common progression models of breast cancer. The detection of genetic alterations within normal breast tissue in particular challenges the commonly postulated relationship between invasive and in situ breast carcinomas on the one hand, and benign, proliferative breast lesions on the other. The concerns about these relationship are further supported by the description of different cellular compartments within the normal female breast, including a "progenitor cell compartment" with different cytokeratin expression patterns, which can be transferred towards well known or suspected precursor lesions of invasive and in situ breast cancer. The aim of this manuscript is to provide an overview of the most recent results and developments in breast pathology, and to describe the consequences of our changing understanding of breast carcinogenesis.
...
PMID:[The significance of "normal tissue" in the development of breast cancer: new concepts of early carcinogenesis]. 1689 74

Interactions between chemokines and chemokine receptors have been proposed recently to be of importance in the development and progression of cancer. Human breast cancer cells express the chemokine CXCL10 (IP-10) and also its receptor CXCR3. In this study, we have investigated the role of Ras activation in the regulation of CXCL10 and its receptor splice variant CXCR3-B in two human breast cancer cell lines MDA-MB-435 and MCF-7. In cotransfection assays, using a full-length CXCL10 promoter-luciferase construct, we found that the activated form of Ras, Ha-Ras(12V), promoted CXCL10 transcriptional activation. Ras significantly increased CXCL10 mRNA and protein expression as observed by real-time PCR, fluorescence-activated cell sorting analysis, and ELISA. Selective inhibition of Ha-Ras by small interfering RNA (siRNA) decreased CXCL10 mRNA expression in a dose-dependent manner. Further, using effector domain mutants of Ras, we found that Ras-induced overexpression of CXCL10 is mediated primarily through the Raf and phosphatidylinositol 3-kinase signaling pathways. We also observed that the expression of the splice variant CXCR3-B, known to inhibit cell proliferation, was significantly down-regulated by Ras. Selective inhibition of CXCR3-B using siRNA resulted in an increase in CXCL10-mediated breast cancer cell proliferation through G(i) proteins and likely involving CXCR3-A. Finally, we observed intense expression of CXCL10 and CXCR3 in association with human breast cancer in situ, indicating that these observations may be of pathophysiologic significance. Together, these results suggest that activation of Ras plays a critical role in modulating the expression of both CXCL10 and CXCR3-B, which may have important consequences in the development of breast tumors through cancer cell proliferation.
...
PMID:Ras-induced modulation of CXCL10 and its receptor splice variant CXCR3-B in MDA-MB-435 and MCF-7 cells: relevance for the development of human breast cancer. 1701 7

Methylenetetrahydrofolate reductase (MTHFR), a key regulatory enzyme in the metabolism of folate, is suspected to play a role in the etiology of cancer, via its effects on DNA methylation and nucleotide synthesis. In this study we have investigated the effect of two functional polymorphisms of the MTHFR gene, MTHFR_677_C > T and MTHFR_1298_A > C, on breast and ovarian cancer risk in Polish BRCA1 mutation carriers. The study included 319 breast cancer cases, 146 ovarian cancer cases and 290 controls unaffected by breast and ovarian cancer, in situ breast cancer or any other kind of cancer. Genotyping analysis was performed using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using univariate and multivariate logistic regression taking into account a series of confounding variables that potentially could have biased any association. The results revealed that the MTHFR_677_C > T change was associated with an increased risk of breast and ovarian cancer. The MTHFR_1298_A > C polymorphism was only associated with a decrease in breast cancer risk. Together, it appears that functional polymorphisms in the MTHFR gene modify the risk of breast and may potentially alter the risk of ovarian cancer in women with an inherited predisposition.
Breast Cancer Res Treat 2007 Sep
PMID:Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks. 1706 64

<< Previous 1 2 3 4 5 6 7 8 9 Next >>