| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Hunter, D J, et al.
(författare)
-
Non-dietary factors as risk factors for breast cancer, and as effect modifiers of the association of fat intake and risk of breast cancer
- 1997
-
Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 8:1, s. 49-56
-
Tidskriftsartikel (refereegranskat)abstract
- To assess more precisely the relative risks associated with established risk factors for breast cancer, and whether the association between dietary fat and breast cancer risk varies according to levels of these risk factors, we pooled primary data from six prospective studies in North America and Western Europe in which individual estimates of dietary fat intake had been obtained by validated food-frequency questionnaires. Based on information from 322,647 women among whom 4,827 cases occurred during follow-up: the multivariate-adjusted risk of late menarche (age 15 years or more compared with under 12) was 0.72 (95 percent confidence interval [CI] = 0.62-0.82); of being postmenopausal was 0.82 (CI = 0.69-0.97); of high parity (three or more births compared with none) was 0.72 (CI = 0.61-0.86); of late age at first birth (over 30 years of age compared with 20 or under) was 1.46 (CI = 1.22-1.75); of benign breast disease was 1.53 (CI = 1.41-1.65); of maternal history of breast cancer was 1.38 (CI = 1.14-1.67); and history of a sister with breast cancer was 1.47 (CI = 1.27-1.70). Greater duration of schooling (more than high-school graduation compared with less than high-school graduation) was associated significantly with higher risk in age-adjusted analyses, but was attenuated after controlling for other risk factors. Total fat intake (adjusted for energy consumption) was not associated significantly with breast cancer risk in any strata of these non-dietary risk factors. We observed a marginally significant interaction between total fat intake and risk of breast cancer according to history of benign breast disease; with fat intake being associated nonsignificantly positively with risk among women with a previous history of benign breast disease; no other significant interactions were observed. Risks for reproductive factors were similar to those observed in case-control studies; relative risks for family history of breast cancer were lower. We found no clear evidence in any subgroups of a major relation between total energy-adjusted fat intake and breast cancer risk.
|
|
| 6. |
|
|
| 7. |
- Petersen, Frank, et al.
(författare)
-
Characterization of a neutophil surfacer glycosaminoglycan responsible for binding of platelet factor 4
- 1999
-
Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 274:18, s. 12376-12382
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract Platelet factor 4 (PF-4) is a platelet-derived α-chemokine that binds to and activates human neutrophils to undergo specific functions like exocytosis or adhesion. PF-4 binding has been shown to be independent of interleukin-8 receptors and could be inhibited by soluble chondroitin sulfate type glycosaminoglycans or by pretreatment of cells with chondroitinase ABC. Here we present evidence that surface-expressed neutrophil glycosaminoglycans are of chondroitin sulfate type and that this species binds to the tetrameric form of PF-4. The glycosaminoglycans consist of a single type of chain with an average molecular mass of ∼23 kDa and are composed of ∼85–90% chondroitin 4-sulfate disaccharide units type CSA (→4GlcAβ1→3GalNAc(4-O-sulfate)β1→) and of ∼10–15% di-O-sulfated disaccharide units. A major part of these di-O-sulfated disaccharide units are CSE units (→4GlcAβ1→3GalNAc(4,6-O-sulfate)β1→). Binding studies revealed that the interaction of chondroitin sulfate with PF-4 required at least 20 monosaccharide units for significant binding. The di-O-sulfated disaccharide units in neutrophil glycosaminoglycans clearly promoted the affinity to PF-4, which showed a K d ∼ 0.8 μm, as the affinities of bovine cartilage chondroitin sulfate A, porcine skin dermatan sulfate, or bovine cartilage chondroitin sulfate C, all consisting exclusively of monosulfated disaccharide units, were found to be 3–5-fold lower. Taken together, our data indicate that chondroitin sulfate chains function as physiologically relevant binding sites for PF-4 on neutrophils and that the affinity of these chains for PF-4 is controlled by their degree of sulfation. The activation and control of polymorphonuclear granulocytes (PMN)1 are known to play an essential role in host defense against microbial invaders as well as in chronic diseases. Several members of the α-chemokine family like interleukin-8 (IL-8), neutrophil-activating peptide 2, or melanoma growth stimulatory activity have been shown to act as potent activators of PMN by binding to common IL-8 receptors (1). Such binding elicits diverse biological responses such as chemotaxis, degranulation, or adhesion. PF-4, another member of the α-subgroup of the chemokine family, is released in high concentrations from activated platelets (2,3). The functional role of PF-4 is intriguing. Highly purified PF-4 lacks any apparent biological activity for PMN but will in the presence of tumor necrosis factor α stimulate these cells to exocytose secondary granule markers or adhere tightly to different surfaces (4). These PF-4-induced functions are not elicited through binding to IL-8 receptors but by interaction with distinct binding sites different from all other chemokine receptors known so far (4,5). The action of PF-4 on PMN was shown to be sensitive to chondroitinase ABC treatment and could be inhibited by soluble chondroitin sulfate (CS), indicating that the potential receptor is of CS proteoglycan type (5). CSs are galactosaminoglycans composed of alternating glucuronic acid and galactosamine units (→4GlcAβ1→3GalNAcβ1→)n that areO-sulfated on one or both units.2 In contrast to the glucosaminoglycans heparin and heparan sulfate (HS), they do not contain N-sulfate groups or l-iduronic acid units (except for CSB), which have been particularly implicated in protein binding to HS chains (6). The expression of glycosaminoglycans (GAGs) on neutrophils has been described previously by several authors. Pioneering work by Olsson and co-workers showed that PMN predominantly express chondroitin 4-sulfate (CSA) (7, 8), and Levitt et al. demonstrated a minor proportion of HS in these cells (9). However, as all of these analyses were done with total cell extracts, little is known about the composition and function of cell surface-expressed GAGs in PMN. Gardiner and colleagues showed that the majority of metabolically 35S-labeled compounds occurs as proteoglycans in neutrophil granules where they may enable proper storage of granule contents or exert protective functions against cellular damage (10,11). Here, we provide evidence that surface exposed CS chains serve as physiologically relevant receptors for PF-4 on PMN, and propose that this function is critically dependent on the content of sulfate groups.
|
|
| 8. |
|
|
| 9. |
- Smith-Warner, Stephanie A., et al.
(författare)
-
Alcohol and breast cancer in women : A pooled analysis of cohort studies
- 1998
-
Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 279:7, s. 535-540
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. DATA SOURCES: We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. DATA EXTRACTION: Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. DATA SYNTHESIS: For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. CONCLUSIONS: Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.
|
|
