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Human Growth Hormone - Can Preoperative Axillary US Help Exclude N2 and N3 Metastatic

basskiller — Fri, 03 Sep 2010 12:10:07 GMT

Radiology. 2010 Aug 31;
Neal CH, Daly CP, Nees AV, Helvie MA
Purpose: To determine the false-negative rate of axillary ultrasonography (US) with respect to stage N2 and N3 metastatic disease in patients with newly diagnosed breast cancer. Materials and Methods: The study was approved by the institutional review board and complied with the HIPAA; the requirement for informed consent was waived. A retrospective search of radiology records identified 435 consecutive patients with breast cancer aged 25-88 years who underwent preoperative axillary US from January 1, 2006, to December 31, 2007. Two hundred five patients (203 women and two men) had 208 negative US scans with correlative surgical and/or pathologic lymph node data. Criteria used to detect abnormal lymph nodes included subjective assessment of diffuse cortical thickening, focal cortical mass/thickening, and replacement or effacement of the fatty hilum. Tumor type, grade, size, and hormone receptor status were documented. Statistical analysis was performed with the Fisher exact test. Results: Of the 208 axillae with negative findings at US, 14 (6.7%) had a final node stage of N2 or N3. Twelve of the 208 axillae (5.8%) had stage N2 disease and two (1.0%) had stage N3 disease. Of the 14 axillae with stage N2 or N3 disease, eight (57.1%) had lobular histologic characteristics and six (42.9%) had ductal histologic characteristics. The false-negative rate for N2 and N3 disease was 4.1% (six of 146 axillae) for invasive ductal cancer and 17% (eight of 47 axillae) for invasive lobular cancer (P < .01). None of the 14 axillae with stage N2 or N3 disease were "triple negative" (ie, estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor type 2 negative). Conclusion: Preoperative axillary US excluded 96% of N2 and N3 invasive ductal metastases. The false-negative rate for N2 and N3 invasive lobular cancer was significantly higher than that for invasive ductal cancer, which suggests that axillary US cannot be used to exclude N2 and N3 metastases in these patients. (c) RSNA, 2010.

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Human Growth Hormone - Parathyroid hormone-potentiated connective tissue growth facto

basskiller — Fri, 03 Sep 2010 12:10:07 GMT

Nephrol Dial Transplant. 2010 Sep 1;
Guo Y, Yuan W, Wang L, Shang M, Peng Y
BACKGROUND: Secondary hyperparathyroidism is a universal complication of chronic renal diseases. One of the pathological consequences of hyperparathyroidism is impairment of the renal interstitium and tubules. However, the molecular mechanism of renal tubular interstitial impairment induced by parathyroid hormone (PTH) remains unclear. Enhanced and prolonged expression of connective tissue growth factor (CTGF) has been associated with fibrosis and inflammation in the kidney. The purpose of this study was to investigate the effects of PTH on CTGF expression patterns in human proximal tubular cell line-HK-2 cells. METHODS: We treated cells with various concentrations of PTH for the indicated periods of time in the presence or absence of the mitogen-activated protein kinase (MAPK) inhibitor (PD98059) or the NF-kappaB inhibitor (PDTC). RESULTS: Quantitative real-time RT-PCR analysis revealed that PTH at a concentration of 10( - )(12)-10( - )(10) M increased the mRNA levels of CTGF, which was similar to the trends of CTGF protein levels detected by immunoblotting assay. Our data clearly show the ability of human proximal tubular HK-2 cells to produce CTGF after the treatment with PTH. In addition, we showed that PTH induced the phosphorylation of MAPK p42 and p44, and increased NF-kappaB-binding activities in the PTH-treated cells. Moreover, both PD98059 and PDTC inhibited the effect of PTH on the expression of CTGF, which strongly suggests that these pathways play important roles in the PTH-induced CTGF upregulation in renal tubular cells. CONCLUSIONS: Our results indicated for the first time that PTH may enhance the expression of CTGF in human kidney proximal tubular cells, suggesting that PTH may play an important role in the fibrotic and inflammatory process that is a hallmark for progression of chronic kidney disease.

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Human Growth Hormone - Significant prognostic factor of immunohistochemical HER-2 exp

basskiller — Fri, 03 Sep 2010 12:10:07 GMT

Prostate. 2010 Sep 1;
Tobiume M, Yamada Y, Nakamura K, Aoki S, Zennami K, Kato Y, Nishikawa G, Yokoi T, Honda N
BACKGROUND: We examined whether human epidermal growth factor-2(HER-2) overexpression could be a useful marker of outcome after hormone therapy in patients with M1b prostate cancer (PC). SUBJECTS AND METHODS: The subjects were 102 patients who were diagnosed with M1b PC at Aichi Medical University Hospital. HER-2 expression was determined by immunohistochemical (IHC) staining using initial needle biopsy specimens for diagnosis. The results were classified into four grades (0, 1+, 2+, 3+), and scores of 1+ or greater were considered overexpression and defined as positive. RESULTS: The results showed a rating of 0 in 72 subjects, 1+ in 10, 2+ in 14, and 3+ in 6; 30 subjects (29.4%) were classified as HER-2 positive. Comparison of clinical data of HER-2 positive and negative subjects obtained at baseline revealed many of the subjects with high-grade tumors by Gleason score were HER-2 positive (P = 0.030). The prostate-specific antigen (PSA) relapse was observed in 76 subjects and cause-specific death occurred in 44. A significant difference was observed only in the item HER-2 (negative vs. positive) by multivariate Cox proportional hazard analysis. The 5-year PSA relapse-free rate was 0% in subjects with HER-2 positive (26/30), and 43.9% in subjects with HER-2 negative (50/72, P = 0.0192). The 5-year cause-specific survival rate was 40.9% in subjects with HER-2 positive (30/102), and 67.3% in subjects with HER-2 negative (72/102, P = 0.0301). CONCLUSION: HER-2 overexpression as determined by IHC staining using needle biopsy specimens for diagnosis with M1b PC is a significant prognostic factor for PSA relapse after hormone therapy and unfavorable outcome. Prostate (c) 2010 Wiley-Liss, Inc.

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Human Growth Hormone - Insulin-like growth factor 1 treatment extends longevity in a

basskiller — Thu, 02 Sep 2010 12:00:04 GMT

Proc Natl Acad Sci U S A. 2010 Aug 30;
Mari�o G, Ugalde AP, Fern�ndez AF, Osorio FG, Fueyo A, Freije JM, L�pez-Ot�n C
Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A, an essential component of the nuclear envelope. Zmpste24-deficient mice exhibit multiple defects that phenocopy human accelerated aging processes such as Hutchinson-Gilford progeria syndrome. In this work, we report that progeroid Zmpste24(-/)(-) mice present profound transcriptional alterations in genes that regulate the somatotroph axis, together with extremely high circulating levels of growth hormone (GH) and a drastic reduction in plasma insulin-like growth factor 1 (IGF-1). We also show that recombinant IGF-1 treatment restores the proper balance between IGF-1 and GH in Zmpste24(-/)(-) mice, delays the onset of many progeroid features, and significantly extends the lifespan of these progeroid animals. Our findings highlight the importance of IGF/GH balance in longevity and may be of therapeutic interest for devastating human progeroid syndromes associated with nuclear envelope abnormalities.

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HGH - Effect of high- and low-intensity exercise and metabolic acidosis on levels of

basskiller — Tue, 31 Aug 2010 11:30:04 GMT

Growth Horm IGF Res. 2010 Aug 26;
Wahl P, Zinner C, Achtzehn S, Bloch W, Mester J
OBJECTIVE: The purpose of the present study was to examine the acute hormonal response of a short term high-intensity training (HIT) versus a high volume endurance training (HVT) and to determine the contribution of the metabolic acidosis as a stimulus for possibly different reactions of circulating hGH, IGF-1, IGFBP-3 and cortisol. DESIGN: Eleven subjects participated in three experimental trials separated by one week. Two times subjects performed four 30s maximal effort exercise bouts on a cycle ergometer separated by 5min rest each. Before the exercise subjects either received (single-blinded) bicarbonate (HIT (B)) or a placebo (HIT (P)). The third exercise trail consisted of a constant load exercise for 1h at 50% VO(2)max (HVT). Venous blood samples were taken under resting conditions, 10min, 60min and 240min after each exercise condition to determine hGH, IGF-1, IGFBP-3 and cortisol serum concentrations. Capillary blood samples were taken to determine lactate concentrations and blood gas parameters. RESULTS: Power output, mean lactate concentrations and mean pH values were significantly higher during HIT (B) compared to HIT (P). Serum cortisol and hGH concentrations were significantly increased 10min post exercise in both HIT interventions. IGFBP-3 was only significantly increased after HIT (P), whereas IGF-1 was not affected by any of the interventions. HVT showed no significant effects on cortisol, hGH, IGF-1 and IGFBP-3 levels. Additionally it was shown that the diminished acidosis during HIT (B) attenuates the cortisol and hGH response. CONCLUSIONS: The present study suggests that HIT/acidosis is a stimulus for exercise-induced cortisol/hGH secretion, but not for IGF-1 and IGFBP-3 under these experimental conditions. These findings might be relevant for arrangements of interval training, due to the fact that active or passive recovery during rest periods influence the acid base status and may therefore influence the hormonal response.

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Human Growth Hormone - Effects of recombinant human growth hormone (rhGH) replacement

basskiller — Tue, 31 Aug 2010 11:30:04 GMT

Neuro Endocrinol Lett. 2010 Aug 30; 31(4):
Szynaka E, Petriczko E, Grabarek J, Miklaszewicz A, Domagala W, Walczak M
OBJECTIVE: This study aims at assessing how recombinant human growth hormone treatment of children and young people suffering from isolated growth hormone deficiency affects some selected parameters of the immune system: a percentage of lymphocytes, granulocytes, monocytes, concentrations of A, G, and M immunoglobulins, a percentage of T lymphocytes divided into subpopulations CD4 and CD8, a percentage of NK and B lymphocytes, and phagocytic activity of granulocytes and monocytes. MATERIALS AND METHODS: The study comprised 30 children and young people aged 4.2-18 years with isolated growth hormone deficiency both prior to and 6 months after rhGH (recombinant human growth hormone) treatment with a dose of 0.093 IU/kg every 24 hr. The control group comprised 25 healthy children with normal height in the respective age bracket. Labelling was conducted by flow cytometry FACS manufactured by Becton-Dickinson using both labelled antibodies and PHAGOTEST(R) commercial kit (Orpegen). Concentrations of A, G and M immunoglobulins in blood serum were assessed by means of immunoturbidimetric method using COBAS (manufactured by Roche). RESULTS: The lowest percentage of active granulocytes in PHAGOTEST(R) was found in a group examined prior to treatment compared to the control group. The percentage increased after 6 months of rhGH treatment to values comparable with the control group. Although mean concentrations of IgM and IgA after 6 months of treatment with rhGH significantly decreased in comparison with those determined prior to treatment, they still remained within the baseline norm.

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Human Growth Hormone - Immunization with a recombinant GnRH vaccine fused to heat sho

basskiller — Tue, 31 Aug 2010 11:30:04 GMT

Cancer Immunol Immunother. 2010 Aug 28;
Wang XJ, Gu K, Xu JS, Li MH, Cao RY, Wu J, Li TM, Liu JJ
Gonadotrophin-releasing hormone (GnRH) is the prime decapeptide hormone in the regulation of mammalian reproduction. Active immunization against GnRH has been a good treatment option to fight against hormone-dependent disease such as breast cancer. We designed and purified a novel protein vaccine Hsp65-GnRH(6) containing heat shock protein 65 (Hsp65) and six copies of GnRH in linear alignment. Immunization with Hsp65-GnRH(6) evoked strong humoral response in female mice. The generation of specific anti-GnRH antibodies was detected by ELISA and verified by western blot. In addition, anti-GnRH antibodies effectively neutralized endogenous GnRH activity in vivo, as demonstrated by the degeneration of the ovaries and uteri in the vaccinated mice. Moreover, the growth of EMT-6 mammary tumor allografts was inhibited by anti-GnRH antibodies. Histological examinations have shown that there was increased focal necrosis in tumors. Taken together, our results showed that immunization with Hsp65-GnRH(6) elicited high titer of specific anti-GnRH antibodies and further led to atrophy of reproductive organs. The specific antibodies could inhibit the growth of EMT-6 murine mammary tumor probably via an indirect mechanism that includes the depletion of estrogen. In view of these results, the protein vaccine Hsp65-GnRH(6) appears to be a promising candidate vaccine for hormone-dependent cancer therapy.

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Human Growth Hormone - Deoxynivalenol: mechanisms of action, human exposure, and toxi

basskiller — Sat, 28 Aug 2010 10:42:29 GMT

Arch Toxicol. 2010 Aug 27;
Pestka JJ
The trichothecene mycotoxin deoxynivalenol (DON) is produced in wheat, barley and corn following infestation by the fungus Fusarium in the field and during storage. Colloquially known as "vomitoxin" because of its emetic effects in pigs, DON has been associated with human gastroenteritis. Since DON is commonly detected in cereal foods, there are significant questions regarding the risks of acute poisoning and chronic effects posed to persons ingesting this trichothecene. A further challenge is how to best manage perceived risks without rendering critical food staples unavailable to an ever-expanding world population. In experimental animal models, acute DON poisoning causes emesis, whereas chronic low-dose exposure elicits anorexia, growth retardation, immunotoxicity as well as impaired reproduction and development resulting from maternal toxicity. Pathophysiologic effects associated with DON include altered neuroendocrine signaling, proinflammatory gene induction, disruption of the growth hormone axis, and altered gut integrity. At the cellular level, DON induces ribotoxic stress thereby disrupting macromolecule synthesis, cell signaling, differentiation, proliferation, and death. There is a need to better understand the mechanistic linkages between these early dose-dependent molecular effects and relevant pathological sequelae. Epidemiological studies are needed to determine if relationships exist between consumption of high DON levels and incidence of both gastroenteritis and potential chronic diseases. From the perspective of human health translation, a particularly exciting development is the availability of biomarkers of exposure (e.g. DON glucuronide) and effect (e.g. IGF1) now make it possible to study the relationship between DON consumption and growth retardation in susceptible human populations such as children and vegetarians. Ultimately, a fusion of basic and translational research is needed to validate or refine existing risk assessments and regulatory standards for this common mycotoxin.

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Human Growth Hormone - Ghrelin cells in the gastrointestinal tract.

basskiller — Sat, 28 Aug 2010 10:42:29 GMT

Int J Pept. 2010; 2010:
Sakata I, Sakai T
Ghrelin is 28-amino-acid peptide that was discovered from the rat and human stomach in 1999. Since the discovery of ghrelin, various functions of ghrelin, including growth hormone release, feeding behavior, glucose metabolism, memory, and also antidepressant effects, have been studied. It has also been reported that ghrelin in the gastrointestinal tract has an important physiological effect on gastric acid secretion and gastrointestinal motility. Ghrelin has a unique structure that is modified by O-acylation with n-octanoic acid at third serine residues, and this modification enzyme has recently been identified and named ghrelin O-acyl transferase (GOAT). Ghrelin is considered to be a gut-brain peptide and is abundantly produced from endocrine cells in the gastrointestinal mucosa. In the gastrointestinal tract, ghrelin cells are most abundant in the stomach and are localized in gastric mucosal layers. Ghrelin cells are also widely distributed throughout the gastrointestinal tract. In addition, abundance of ghrelin cells in the gastric mucosa is evolutionally conserved from mammals to lower vertebrates, indicating that gastric ghrelin plays important roles for fundamental physiological functions. Ghrelin cells in the gastrointestinal tract are a major source of circulating plasma ghrelin, and thus understanding the physiology of these cells would reveal the biological significance of ghrelin.

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Human Growth Hormone - Quality of Life in Hormone Receptor-Positive HER-2+ Metastatic

basskiller — Sat, 28 Aug 2010 10:42:29 GMT

Oncologist. 2010 Aug 26;
Sherrill B, Amonkar MM, Sherif B, Maltzman J, O'Rourke L, Johnston S
Abstract Background. A phase III trial compared lapatinib plus letrozole (L + Let) with letrozole plus placebo (Let) as first-line therapy for hormone receptor (HR)(+) metastatic breast cancer (MBC) patients. The primary endpoint of progression-free survival (PFS) in patients whose tumors were human epidermal growth factor receptor (HER)-2(+) was significantly longer for L + Let than for Let (8.2 months versus 3 months; p = .019). This analysis focuses on quality of life (QOL) in the HER-2(+) population. Methods. QOL was assessed at screening, every 12 weeks, and at withdrawal using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Changes from baseline were analyzed and the proportions of patients achieving minimally important differences in QOL scores were compared. Additional exploratory analyses evaluated how QOL changes reflected tumor progression status. Results. Among the 1,286 patients randomized, 219 had HER-2(+) tumors. Baseline QOL scores were comparable in the two arms. Mean changes in QOL scores were generally stable over time for patients who stayed on study. The average change from baseline on the FACT-B total score in both arms was positive at all scheduled visits through week 48. There was no significant difference between the two treatment arms in the percentage of QOL responders. Conclusion. The addition of lapatinib to letrozole led to a significantly longer PFS interval while maintaining QOL during treatment, when compared with letrozole alone, thus confirming the clinical benefit of the combination therapy in the HR(+) HER-2(+) MBC patient population. This all oral regimen provides an effective option in this patient population, delaying the need for chemotherapy and its accompanying side effects.

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Human Growth Hormone - Excipient exchange in the comparison of preparations of the sa

basskiller — Sat, 28 Aug 2010 10:42:29 GMT

Biologicals. 2010 Aug 24;
Cauchy M, Hefford MA
Demonstrations of bio-similarity between subsequent entry (follow-on) biologics and innovator's formulated drug products may depend upon methods that either remove excipients completely or allow the exchange of excipients to give equivalent formulations. Excipient exchange through dialysis is perhaps the simplest of such methods but its use has been hotly debated. This debate, in the absence of published data, has relied largely on theoretical considerations. This study presents data that indicate that excipient exchange can allow comparisons of different formulations of the same therapeutic protein. The use of excipient exchange to and from one concentration of mannitol to another or to a mixture of glycine and mannitol was reproducibly demonstrated for recombinant human growth hormone (rhGH). We show that marketed rhGH products from several different manufacturers exhibit differences in conformational stability when compared directly. These differences, however, are shown to be the result of differences in formulation rather than in the drug substance itself and were removed through excipient exchange. The data presented, therefore, also indicate that failure to assure a common excipient background can lead to erroneous conclusions about the similarities and differences in the physico-chemical properties of two preparations of the same therapeutic protein made by different manufacturing processes.

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Human Growth Hormone - Natriuretic Peptides in the Regulation of the Hypothalamic-Pit

basskiller — Sat, 28 Aug 2010 10:42:29 GMT

Int Rev Cell Mol Biol. 2010; 280C: 1-39
Porzionato A, Macchi V, Rucinski M, Malendowicz LK, De Caro R
Atrial (ANP), brain (BNP), and C-type (CNP) natriuretic peptides act by binding to three main subtypes of receptors, named NPR-A, -B, and -C. NPR-A and NPR-B are coupled with guanylate cyclase. Not only NPR-C is involved in removing natriuretic peptides from the circulation but it also acts through inhibition of adenylyl cyclase. NPR-A binds ANP and BNP; NPR-B preferentially binds CNP; and NPR-C binds all natriuretic peptides with similar affinities. All natriuretic peptides and their receptors are widely present in the hypothalamus, pituitary, adrenal cortex, and medulla. In the hypothalamus, they reduce norepinephrine release, inhibit oxytocin, vasopressin, corticotropin-releasing factor, and luteinizing hormone-releasing hormone release. In the hypophysis, natriuretic peptides inhibit basal and induced ACTH release. Conversely, the effects of natriuretic peptides on secretion of growth, luteinizing, and follicle-stimulating hormones are not clear. Natriuretic peptides are known to inhibit basal and stimulated aldosterone secretion, through an increase of intracellular cGMP, and to inhibit the growth of zona glomerulosa. Inhibition or stimulation of glucocorticoid secretion by adrenocortical cells has been reported on the basis of the species involved, and an indirect effect mediated by adrenalmedullary cells has been hypothesized. In the adrenal medulla, natriuretic peptides inhibit catecholamine release and increase catecholamine uptake. It appears that natriuretic peptides may play a role in the pathophysiology of adrenocortical neoplasias and pheochromocytomas.

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Human Growth Hormone - Treatment with growth hormone, somatostatin, and insulin in co

basskiller — Fri, 27 Aug 2010 10:31:01 GMT

Nutrition. 2010 Aug 24;
Liu Q, Liu Z, Chen H, Ma L, Liu L, Zhang J, He Y, Chen J, Qian Q
OBJECTIVE: The metabolic response to gastrointestinal cancer in patients undergoing surgery is associated with hypermetabolism and insulin resistance. The potential use of synergetic anabolic hormones in conjunction with hypocaloric parenteral nutrition (HPN) has become a significant area of investigation. The presented study was performed to determine the clinical efficiency and safety of hormone therapy combined with HPN in patients with gastrointestinal cancer. METHODS: One hundred patients with a Nutrition Risk Screening score of 3 or 4 undergoing surgery for gastrointestinal cancer were randomized into two groups. The patients in the control group received standard total parenteral nutrition and systemic insulin. The patients in the study group received HPN and systemic insulin in addition to pretreatment with recombinant human growth hormone and octreotide. Clinical efficiency and safety were evaluated by the measurement of hormones and protein metabolites, immune function, clinical outcome, and adverse events. Follow-ups were performed to determine the influence on prognosis. RESULTS: Treatment with recombinant human growth hormone, octreotide, and insulin in combination with HPN significantly increased protein synthesis, immune function, and metabolic tolerance, decreased infectious complications, and shortened postoperative hospital stays, but did not increase the risk of tumor development and recurrence in the study group compared with the control group. CONCLUSION: The proper short-term perioperative administration of growth hormone, somatostatin, and insulin in combination with HPN can overcome the postoperative stress response through the increase of protein synthesis to improve immune function in patients with gastrointestinal cancer after surgery.

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Human Growth Hormone - Odyssey of Auxin.

basskiller — Fri, 27 Aug 2010 10:31:01 GMT

Cold Spring Harb Perspect Biol. 2010 Aug 25;
Abel S, Theologis A
The history of plant biology is inexorably intertwined with the conception and discovery of auxin, followed by the many decades of research to comprehend its action during growth and development. Growth responses to auxin are complex and require the coordination of auxin production, transport, and perception. In this overview of past auxin research, we limit our discourse to the mechanism of auxin action. We attempt to trace the almost epic voyage from the birth of the hormonal concept in plants to the recent crystallographic studies that resolved the TIR1-auxin receptor complex, the first structural model of a plant hormone receptor. The century-long endeavor is a beautiful illustration of the power of scientific reasoning and human intuition, but it also brings to light the fact that decisive progress is made when new technologies emerge and disciplines unite.

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Human Growth Hormone - Prolactin serum levels and breast cancer: relationships with r

basskiller — Thu, 26 Aug 2010 10:30:21 GMT

Br J Cancer. 2010 Aug 24;
Faupel-Badger JM, Sherman ME, Garcia-Closas M, Gaudet MM, Falk RT, Andaya A, Pfeiffer RM, Yang XR, Lissowska J, Brinton LA, Peplonska B, Vonderhaar BK, Figueroa JD
Background:Previous prospective studies have found an association between prolactin (PRL) levels and increased risk of breast cancer. Using data from a population-based breast cancer case-control study conducted in two cities in Poland (2000-2003), we examined the association of PRL levels with breast cancer risk factors among controls and with tumour characteristics among the cases.Methods:We analysed PRL serum levels among 773 controls without breast cancer matched on age and residence to 776 invasive breast cancer cases with available pretreatment serum. Tumours were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis. Breast cancer risk factors, assessed by interview, were related to serum PRL levels among controls using analysis of variance. Mean serum PRL levels by tumour characteristics are reported. These associations also were evaluated using polytomous logistic regression.Results:Prolactin levels were associated with nulliparity in premenopausal (P=0.05) but not in postmenopausal women. Associations in postmenopausal women included an inverse association with increasing body mass index (P=0.0008) and direct association with use of recent/current hormone therapy (P=0.0006). In case-only analyses, higher PRL levels were more strongly associated with lobular compared with ductal carcinoma among postmenopausal women (P=0.02). Levels were not different by tumour size, grade, node involvement or oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status.Conclusions:Our analysis demonstrates that PRL levels are higher among premenopausal nulliparous as compared with parous women. Among postmenopausal women, levels were higher among hormone users and lower among obese women. These results may have value in understanding the mechanisms underlying several breast cancer risk factor associations.British Journal of Cancer advance online publication, 24 August 2010; doi:10.1038/sj.bjc.6605844 www.bjcancer.com.

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