Study Suggests IGF-1 Plays ‘Causal Role’ in Breast Cancer

Ladies with excessive amounts of insulin-like growth factor 1 (IGF-1) may be at elevated risk for breast cancer, as outlined by outcomes of a study that used both epidemiological techniques as well as genetic analyses.

The outcome was published online March 11 in Annals of Oncology

“Taken together, these results provide the strongest evidence to date for a causal role of the IGF-pathway in breast cancer development,” said senior author Marc Gunter, PhD, head of the nutritional epidemiology group at the International Agency for Research on Cancer (IARC) in Lyon, France.

The final results likewise “declare that modifying IGF-1 levels with the aid of diet and lifestyle or pharmacological techniques may be a powerful strategy in the main prevention of breast cancer,” he added in a press statement.

A growth hormone referred to as insulin-like growth factor-1 (IGF-1) is more likely to play a role in the advancement breast cancer, as stated by new research published in the leading cancer journal Annals of Oncology [1] today (Wednesday).

IGF-1 is already known to encourage the growth and proliferation of cancer cells. Now, two analyses of information from several hundred thousand women enrolled in the UK Biobank study have shown that not only is there an association between higher levels of IGF-1 circulating in the blood and the development of breast cancer, but also, for the first time, that IGF-1 is likely to be a cause of the disease.

Researchers from the International Agency for Research on Cancer (IARC), Lyon, France, and the Cancer Epidemiology Unit at the University of Oxford, UK, carried out two, complementary studies to investigate the role of IGF-1 in breast cancer development. The first looked at the associations between levels of IGF-1 in the blood and the chances of the disease developing in 206,263 women.

The second study used a technique called Mendelian randomisation to analyse data from 265 variants of genes (single nucleotide polymorphisms or “SNPs”) known to be associated with IGF-1 concentrations in 122,977 cases of breast cancer and 105,974 women without cancer (the controls). In this analysis, the researchers also looked at four SNPs for insulin-like growth factor-binding protein-3 (IGFBP-3), which may modulate the availability of IGF-1.

IGF-1 Increased by Many Factors, Including Milk

IGF-1 is a hormone that is a lot like insulin and enables promotion of body growth, specifically during puberty. The hormone possesses wide-ranging impacts and induces growth of various sorts of cells in your body. Several essentials may possibly boost IGF-1 levels, together with a high-protein diet, pregnancy, and some disease operations, the experts note.

Lately, a few researchers have been enthusiastic about IGF-1 because of a conceivable link between cow’s milk and breast cancer. Dairy cows have been bred to have excessive levels of IGF-1. Most are also pregnant and, by definition, lactating. So the milk they generate has increased amounts of progestins and estrogen. Experts have speculated that excessive levels of IGF-1, estrogen, and progestins in cow’s milk may be involved in the development of breast cancer, as recently reported by Medscape Medical News.

Read more on Milk causing cancer.

Largest Study to Date

“To our knowledge, this is largest single study and the first Mendelian randomization study to examine the relationship between IGF-1 and breast cancer,” Gunter said.

Mendelian randomization uses complex statistical techniques to evaluate genes and their causal effect on disease. In this case, researchers evaluated genes related to IGF-1 levels, and whether variations in these genes were linked to different risks for breast cancer.

“Our Mendelian randomization analyses yielded strikingly similar positive associations between IGF-1 and breast cancer as those found in our observational analyses,” Gunter said.

“The association between IGF-1 and breast cancer was first investigated in the 1980s, and our findings are in line with various studies since then. But clarifying the direction of the association using Mendelian randomization in our study leads the way for research into how the IGF-1 pathway can be harnessed in breast cancer prevention,” coauthor Anika Knüppel, PhD, said in the same press statement. Knüppel is a nutritional epidemiologist at the University of Oxford, United Kingdom.

The next step is to investigate lifestyle factors that may affect IGF-1 levels, and how changing these factors could decrease breast cancer risk. Drugs may also affect IGF-1 levels, but their safety, effectiveness, and length of use would need more study, according to the authors.

Study Details

Journal of Clinical Oncology. (G) Aftereffect of z-VAD-FMK on SNG-induced DNA harm. Breast cancer. The most typical of each is normally IGF-1 and the IGR-1R (R for receptor), respectively. Furthermore, the info of this article also claim that the dosage of rhGH could be a factor worth taking into consideration if rhGH can be used to cancer sufferers without GHR expression. Strategies: Experimental analysis regarding chromosome immunoprecipitation (ChIP) and luciferase reporter assays were utilized to validate hypoxia inducible aspect-1alpha (HIF-1α) as a transcriptional regulator of TWIST1 and Snail. #269. The usage of neoadjuvant therapy can be an intriguing area of analysis in pancreatic cancer tumor. Neuhaus P, Riess H, Post S, et al. CONKO-001: benefits of the randomized, potential, multicenter stage III trial of adjuvant chemotherapy with gemcitabine versus observation in sufferers with resected pancreatic cancer.

Clinical studies also show that metformin reduces insulin level of resistance and increases comprehensive tumor response prices following neoadjuvant chemotherapy for breasts cancer (Jiralerspong 2009). 27:15s. To look for the aftereffect of forced expression of hGH on the CSC-like properties of HCC cells, Huh7 and Hep3B cells with forced expression of hGH had been cultured under ultra-low attachment conditions. Additionally it is an accepted and clinically-proved treatment in building and keeping muscle tissue due to wasting diseases such as for example AIDS and Prader-Willi syndrome.

Release of growth hormones from the pituitary indicators to the liver to secrete IGF-1, which in turn commands the growth of just about any cell in your body, including bones, cartilage, muscle groups, nerves, bloodstream cells, and organs. Various research indicate that milk protein, such as for example casein and specifically whey proteins, may drive back some cancers such as for example colon, breasts, and prostate gland (Parodi 2007 ). The anticancer properties of bovine whey proteins could be attributed to their capability to increase cellular degrees of glutathione, an antioxidant. Extra leucine (and protein and proteins in general) may potentially fuel cancer growth, but can be vital for regular physiologic function, especially in people that are obese.

With a personalized genomic strategy, a combined mix of multiple targeted therapies is most probably to work for patients whose tumors have already been analyzed and proven to have particular markers (e.g., Kras, p53, Her2 etc.) that may actually be targeted. Do it again sequencing analysis could possibly be performed at regular intervals during treatment, or if brand-new metastases or recurrent disease happened, and treatment could possibly be changed accordingly to consider any genetic differences between your original tumor and metastatic cancer tumor cells.

Multiple factors, including a complicated and badly understood pathophysiology and problems in early detection and medical diagnosis make effective treatment of pancreatic cancer incredibly challenging. Pancreatic cancer is normally not detected until it has reached a locally advanced or metastatic stage because of the relative insufficient symptoms in early disease. Current regular of care comprises procedure if the tumor is included within the pancreas, accompanied by adjuvant chemotherapy and perhaps radiation. However, if the malignancy has spread, conventional treatment is bound, and long-term survival prices remain very low.

Dr. Roger Abs, former mind of the Division of Endocrinology at University Medical center of Antwerp, Belgium mentioned that HGH insufficiency among pediatric malignancy survivors who experienced received radiation contact with the pituitary gland or hypothalamus is usually common. Outcomes shown in the Childhood Malignancy Survivor Study (CCSS) disputed a rise in the chance of developing meningioma or glioma. Consequently, HGH therapy is regarded as valuable to improve the standard of life in patients with hgh deficiency following cancer treatment. The info in the statement supports the safety and make use of for adult HGH treatment for childhood mind tumor survivors. With the plethora of study already done on children, additionally it is secure to translate this data to adults who’ve been successfully treated for cancer.

Although we understand the feasible benefits of some option, complementary, or holistic treatment, this site is not strongly oriented in this manner. On an anecdotal basis, we’ve heard about positive experiences that patients experienced with the treating symptoms related to pancreatic malignancy (and chemotherapy) involving such methods as visualization methods, meditation, prayer, acupuncture, therapeutic massage, biofeedback, rest therapy, hypnotherapy acupuncture, green tea extract and Chinese herbs.

Results from the Mendelian randomisation study were similar. For every additional genetically predicted 5 nmol/L of IGF-1, the risk of breast cancer increased by 1.05. However, when the researchers looked at oestrogen receptor positive (ER+) and negative (ER-) breast cancers [2] separately, IGF-1 was only associated with an increased risk of ER+ breast cancer. For every additional 5 nmol/L of IGF-1, there was a 1.06-fold increased risk of ER+ breast cancer. No association was found for IGFBP-3 concentrations and breast cancer risk.

Dr Neil Murphy, a scientist at IARC, said: “We found that higher levels of IGF-1 circulating in the blood, as determined by blood measurements and genetic markers, were related to higher breast cancer risk. These results support a probable causal role of the IGF pathway in breast cancer development.”

Estradiol receptor (ER) and progesterone receptor (PR) expression was evaluated in 27 RCCs so that they can predict the response to progestational therapy. Individuals whose tumors had been positive either for ER or PR (or both) experienced favorable outcomes from progestational therapy. Three individuals with ER-PR-renal cancer showed unfavorable results in follow-up therapy ( 12 ). In the analysis of McDonald et al ( 13 ), PR was measured in eight RCCs in comparison to nine normal renal cells and one melanoma cells sample. PR was identified in every of the samples, apart from one RCC. Three patients, most of whom had receptor-positive tumors, had been treated with medroxyprogesterone acetate for metastatic disease. In another of these patients, a target response to treatment was accomplished. Nakano et al ( 104 ) also demonstrated that hormonal manipulation in individuals with one, or even more receptors, results in a considerably higher survival rate.

Study Suggests IGF-1 Plays ‘Causal Role’ in Breast Cancer

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