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Insulin-like Growth Factor (IGF) and Prostate Cancer
Recent research has found that Insulin-like Growth Factor-1 (IGF-1)
is associated with a significantly increased risk of prostate cancer in
men with the highest levels of IGF-1, compared with those with the lowest
levels. According to the report, men with the highest levels had a 4.3-fold
increased risk of prostate cancer compared with those who had the lowest
IGF-1 levels.
IGF-1 is a growth factor, or hormone, known to stimulate growth and
inhibit death in normal and cancerous prostate cells. The net effect of
this growth factor is to increase the likelihood of mutations in prostate
cells, then to protect the mutated cells from programmed cell death, the
body's natural mechanism for ridding itself of dysfunctional cells. (Sources:
websites listed under Links.)
Results have been mixed, but PCBs have been shown to elevate IGF-1 levels
under some circumstances, which may increase a man’s prostate cancer risk.
More studies are needed.
Studies Related to IGF-1 Levels and Possible PCB Effects
Study #1
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PCBs altered IGF-1 levels in children
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maternal PCB consumption during pregnancy correlated with higher IGF-1
levels in boys
Whale blubber (fat) contains very high concentrations of persistent organochlorine
compounds such as PCB and DDE, some of which are suspected to act as hormone
disruptors. The Faroe Islands is a fishing community in the North Atlantic.
In addition to a high average intake of fish, the faroese also eat pilot
whale and whale blubber. We decided to study if maternal intake of whale
meat and blubber during pregnancy affected hormonal parameters in children.
Methods: The children were part of a birth cohort generated in 1986 in
the Faroe Islands and were examined at 7 years of age. The children were
examined by the same observer (NS) and non-fasting blood samples were drawn
on 273 children (150 boys, 123 girls). We measured IGF-I by a specific
radioimmunoassay. Results: We found significantly higher IGF-I levels
in girls compared to boys (170 (42) vs. 119 (52) ug/L, mean (SD), p
less than 0.0001). Interestingly, the monthly number of maternal whale
dinners during pregnancy correlated significantly negatively with
serum IGF-I levels in the 7-year old girls (Rs = -0.18, p = 0.036),
whereas this correlation was positive and almost reached significance
in boys (Rs = 0.12, p = 0.14). Circulating IGF-I levels correlated
significantly with standing height, weight and body mass index in both
sexes (all p less than 0.02). Conclusion: We found that maternal marine
food intake, and consequently prenatal exposure to PCB and DDE,
were significantly associated with serum IGF-I in 7-year old children.
We speculate that the demonstrated sex difference could be due to different
effects in boys and girls of environmental hormone-disrupting toxicants
present in the whale fat. (Juul et al, 1996)
Study #2
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high levels of insulin-like growth factor 1 (IGF-1) are associated with
prostate cancer
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low levels of vitamin D are associated with prostate cancer
High circulating levels of insulin-like growth factor 1 (IGF-1) or low
levels of 1,25(OH)2 vitamin D (1,25(OH)2D) are associated with an increased
risk of prostate cancer. This project examines whether specific dietary
patterns are related to prostate cancer by influencing levels of IGF-1
and 1 ,25(OH)2D; specifically whether high energy and protein intakes increase
IGF-1 and high intakes of calcium, phosphorus, and animal protein decrease
1 ,25(OH)2D levels. The relationships between dietary factors and circulating
IGF-1 and 1,25(OH)2D are being examined using the Massachusetts Male Aging
Study, for which dietary data and blood samples have already been collected.
(Giovannucci, 1999)
Study #3
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IGF-I concentrations in birds were unaffected by certain types of PCBs
Polychlorinated biphenyls (PCB) are ubiquitous environmental contaminants
that bioaccumulate in avian species. Exposure to PCBs can result in decreased
growth. Thyroid hormones and growth hormone (GH) are important for normal
growth. The present studies employed the chicken embryo to investigate
effects of Aroclor 1242, Aroclor 1254, 2,2',6,6'-tetrachlorobiphenyl (TCB),
3,3',4,4'-TCB, and 3,3',5,5'-TCB on growth and growth-related hormones.
The following indices were measured: embryo mortality, body weights, bone
length, pituitary GH content, and plasma concentrations of triiodothyronine
(T3), thyroxine (T4), GH, and insulin-like growth factor-1 (IGF-1). Fertile
eggs were injected with PCBs on Day 0 and indices determined on Day 17
of incubation. Unexpectedly, 3,3',5,5'-TCB or low-dose Aroclor 1242 treatment
increased body weight and bone length (P < 0.05), whereas Aroclor 1242
(high dose), 3,3,4,4'-TCB, or Aroclor 1254 treatment reduced body weights
and/or bone length (P < 0.05). Aroclor 1242 or 3,3',4,4'-TCB (low-dose
treatment) elevated plasma T4 concentrations (P < 0.05). Both growth
and pituitary GH content were increased (P < 0.05) by 3,3',5,5'-TCB
(low dose) or Aroclor 1242 treatment. Despite marked differences in growth
rates, plasma T3, GH, and IGF-I concentrations were unaffected by PCB
treatment. Growth-related hormones may not be responsible for the growth
depression observed after PCB treatment. Possibly the decrease in growth
occurred because of general toxicity. The importance of chlorine position
in causing thyroid hormone axis alterations was not clearly established.
(Gould et al, 1997)
Upcoming Research
STANFORD JL. GENETIC POLYMORPHISMS AND PROSTATE CANCER RISK. Crisp Data
Base National Institutes of Health. Author Address: FRED HUTCHINSON CANCER
RES CTR, 1100 FAIRVIEW AVE, NORTH, SEATTLE, WA 98109-1024
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both genetic and environmental factors are involved in the causation of
prostate cancer
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insulin-like growth factor-1 (IGF-1) may be involved in prostate cancer
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androgen receptor (AR) changes may be involved in prostate cancer
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vitamin D may be involved in prostate cancer
Prostate cancer is the most frequently diagnosed solid tumor in men, but
aside from age, race, and a family history of the disease, little is known
about the risk factors or underlying molecular defects that cause prostate
cancer. It is clear, however, that both genetic and environmental factors
are involved in the etiology of this complex disease. Genetic studies
are focused on identification o f rare, high-penetrant hereditary prostate
cancer genes and more frequent genetic polymorphisms thought to account
for a higher proportion of the disease in the population and to be involved
in gene-environment interactions. Toward the latter focus, the proposed
study will investigate polymorphism in three genes involved in prostatic
cell proliferation: insulin-like growth factor-1 (IGF-1), androgen receptor
(AR), and vitamin D (VDR). Constitutional DNA will be used to genotype
prostate cancer cases (n=648) and controls (n=571) to test the following
hypotheses: 1) Heterozygosity for a CA repeat in the IGF-1 gene is associated
with increased risk; 2) Short polyglutamine (CAG)n repeats in the AR gene
are associated with enhanced risk; 3) Short polyglycine (GGN)n repeats
in the AR gene are associated with enhanced risk; 4) Long poly-A alleles
in the VDR gene are associated with increased risk; and 5) Homozygosity
for the b allele in the VDR BsmI polymorphism is associated with elevated
risk. Stored blood samples from a population-based case-control study of
prostate cancer are available for the proposed study. Logistic regression
will be used to estimate the relative risk of prostate cancer associated
with each genotype. Data on host and environmental factors will be utilized
to assess whether the strength of the associations with genotype vary by
other factors such as family history or dietary fat intake. Plasma IGF
-1 will be measured in controls to assess correlations between IGF-1 levels
and IGF-1 genotype, and host and environmental exposures. The proposed
study may provide clues on molecular markers that identify men at high
risk of prostate cancer, increase our knowledge of the molecular biology
of this disease, and identify new approaches to prostate cancer prevention.
BURCHIEL SW. MAMMARY CELL SIGNALING PRODUCED BY ENVIRONMENTAL AGENTS.
Crisp Data Base National Institutes Of Health. Author Address: UNIVERSITY
OF NEW MEXICO, COL OF PHARMACY/2502 MARBLE, N, ALBUQUERQUE, NM 87131
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environmental and dietary agents may disrupt normal growth factor signaling
processes, or at low doses may actually mimic signals generated by endogenous
growth factors
The incidence of breast cancer has been increasing in the U.S. and other
countries for many years. While there is no proven explanation for this
increased risk of disease. It appears that environmental and dietary factors
may play an important role in breast cancer development. The purpose of
this proposal is to examine the influence of environmental chemicals on
breast epithelial cell growth and signaling associated with endogenous
growth factor receptors. It is hypothesized that environmental and dietary
agents may disrupt normal growth factor signaling processes, or at low
doses may actually mimic signals generated by endogenous growth factors.
Altered responses to endogenous growth factors may play an important role
in breast cancer development. We will focus on two important class of environmental
agents known as polycyclic aromatic hydrocarbons (PAHs) and halogenated
aromatic hydrocarbon (HAHs) that are present in the air from various emissions
and in the diet. PAHs have been shown by the PI to dramatically alter Ca2+-dependent
cell signaling in human B and T lymphocytes, and recent studies demonstrate
that Ca2+ signaling in human breast epithelial cells is extremely sensitive
to activation by PAHs. Since HAHs share may properties with PAHs, we will
examine this important class of environmental pollutants (including dioxins,
PCBs, and complex mixtures) in this application. We will study PAHs that
are well known mammary carcinogens in animals, and HAHs that are suspected
tumor promoters. Preliminary studies have shown in human lymphoid cell
lines that PAHs exert important effects on Ca2+ homeostasis via activation
of enzymes associated with cell signaling (protein tyrosine kinases) as
well as those involved in regulation of intracellular Ca2+ homeostasis
(Ca2+-ATPase). Many of these same types of enzymes found in lymphocytes
also occur in human breast epithelial cells. Therefore, it is likely that
breast epithelial cell protein tyrosine kinases (EGFR, IGF-1R, and HER-2/erbB-2)
are activated by PAHs. Intracellular Ca2+ measurements will be obtained
using fluorescent Ca2+ chelating agents (Fluo-3) via flow cytometry and
confocal imaging. We will also examine the influence of PAHs and HAHs on
cyclic AMP signaling pathways in human breast cell lines and primary breast
epithelial cell cultures. The influence of estrogenic and anti-estrogenic
chemicals on PAH and HAH-induced signaling will also be explored. The results
of these studies will provide important new information on potential mechanisms
of mimicry or modulation of breast epithelial cell growth factor receptors
and Ca2+ signaling produced by environmental agents.
Go to:
Introduction
Studies Linking
Prostate Cancer and PCBs
Glutathione,
Prostate Cancer and PCBs
Studies Showing
PCBs Alter Key Hormone Levels
Dioxin and
Prostate Cancer
Links to More
Information
References
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