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Iodine Research

Resource Network of The Iodine Movement


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                                      Iodine and the Body

Gastrointestinal

ABNET
Self-reported goiter is associated with a significantly increased risk of gastric noncardia
adenocarcinoma in a large population-based Chinese cohort.
Abnet CC, Fan JH, Kamangar F, Sun XD, Taylor PR, Ren JS, Mark SD, Zhao P, Fraumeni JF, Qiao
YL, Dawsey SM
Int J Cancer. 2006 Apr 26

Iodine is concentrated by the gastric mucosa, where it may act as an antioxidant. Therefore, iodine
deficiency, and its sequelae goiter, may be associated with an increased risk of gastric cancer. We
examined the association between self-reported goiter and upper gastrointestinal cancer in a Chinese
cohort of 29,584 adults. Using multivariate adjusted Cox models, we found goiter associated with a
significantly increased risk of gastric noncardia adenocarcinoma, HR (95% CI) 2.04 (1.01, 4.11) and
nonsignificantly with gastric cardia adenocarcinoma, HR (95% CI) 1.45 (0.91, 2.30). We also found a
borderline, insignificant increased risk of esophageal squamous cell carcinoma, HR (95% CI) 1.37
(0.97, 1.94). Our findings are consistent with the hypothesis that iodine deficiency is associated with
an increased risk of gastric cancer.

ALTORJAY, CARRASCO
Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in gastric cancer and
intestinal metaplastic mucosa of Barrett esophagus
Altorjay A, Dohán O, Szilágyi A, Paroder M, Irene L. Wapnir IL, Carrasco N
BMC Cancer 2007, 7:5.

Background: The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates
iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS
expression and regulation have been extensively investigated in healthy and neoplastic thyroid and
breast tissues, little is known about NIS expression and function along the healthy and diseased
gastrointestinal tract.

Methods: Thus, we investigated NIS expression by immunohistochemical analysis in 155
gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients.

Results: Regarding the healthy GI tract, we observed NIS expression exclusively in the basolateral
region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in
these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was
absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was
detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression
becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional
and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with
intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps.

Conclusions: That NIS expression is markedly decreased or absent in case of intestinalization or
malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor
marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as
Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.

BEHROUZIAN
Urinary iodine/creatinine ratio in patients with stomach cancer in Urmia, Islamic Republic of Iran
Behrouzian R, Aghdami N.
East Mediterr Health J. 2004 Nov;10(6):921-4.

We carried out a case-control study is to investigate the relationship between iodine deficiency and
stomach cancer. We compared the ratio of urinary iodine to urinary creatinine in 100 patients
diagnosed with stomach cancer and 84 people in a control group. Mean urinary iodine levels were
lower in the patients with stomach cancer, 61.9 microg/g creatinine, compared to 101.7 microg/g
creatinine in the control group (P < 0.0001). More of the cancer patients (49.0%) had severe iodine
deficiency (< 25 microg/g creatinine) than people in the control group (19.1%) (P< 0.0001). We found
the relationship between stomach cancer and iodine deficiency to be significant.

GULABOGLU
Comparison of iodine contents in gastric cancer and surrounding normal tissues
Gulaboglu M, Yildiz L, Celebi F, Gul M, Peker K
Clin Chem Lab Med. 2005;43(6):581-4.

It has been suggested that iodine plays an important role in gastric cancer. Gastric cancer ranks first
among the cancers in the north-eastern Anatolia region, Turkey, where iodine deficiency is common.
In this study, iodine levels were determined in gastric cancer and surrounding normal tissues in 19
patients with gastric cancer. Tissue iodine levels were determined by the Foss method based on the
Sandell-Kolt-hoff reaction. Tissue iodine levels were lower in gastric cancer tissue (17.8+/-3.4 ng I/mg
protein, mean+/-SEM) compared with surrounding normal tissue (41.7+/-8.0 ng I/mg protein) (p<0.
001). There was positive correlation between the iodine levels in gastric cancer tissue and
surrounding normal tissue (r = 0.845, p<0.001). There was no significant difference in iodine levels in
cancer and surrounding normal tissue between male and female subjects. The iodine deficiency in our
region may be one of the factors for increased gastric cancer prevalence. Our results support the
hypothesis that iodine plays an important role in gastric cancer development.

KANDEMIR
Gastric carcinoma and thyroid status
Kandemir EG, Yonem A, Narin Y
J Int Med Res. 2005 Mar-Apr;33(2):222-7.

Gastric carcinoma is reported to be more frequent in geographical areas where diets are either iodine-
deficient or iodine-excessive. Reports have also shown an association between thyroid diseases and
some of the risk factors for gastric carcinoma. We investigated the frequency of thyroid disorders in
61 patients with gastric carcinoma compared with 55 healthy control subjects. Thyroid health was
evaluated by physical examination and by measuring the serum levels of thyroid hormones and
thyroid autoantibodies. More patients with gastric cancer had goitre compared with healthy controls
(49.1% versus 20%, respectively). Significantly more patients with gastric cancer had non-toxic goitre
compared with control subjects. There was also a significant difference in the incidence of
autoimmune thyroid disease--27.8% of patients with gastric cancer versus 10.9% of control subjects
were affected. These results indicate that there is a significant association between gastric cancer
and thyroid disorders.

SZYBINSKI
Is iodine prophylaxis (IP) a protective factor against gastric cancer in iodine deficient areas?
Szybinski Z, Rachtan J, Huszno B, Hubalewska A, Buziak-Bereza M, Trofimiuk M
30th Annual Meeting Of European Thyroid Association
Istanbul, Turkey, 18-22 September 2004

Epidemiological data reveal an association between gastric cancer incidence rate (GCIR) and iodine
deficiency (ID) in endemic goiter areas. The “Venturi hypothesis” is based on the correlation between
ID and high GC mortality rate due to common derivation of thyroid gland and stomach from primitive
gut. Gastric mucosa and thyroid folliculi can accumulate iodine, have similar enzymes involved in
iodine metabolism, are able to iodise tyrosine and express similar cross-reacting antigens….
CONCLUSIONS:  Significant positive correlation between iodine nutrition on the population level and
decrease of GCIR seems to support “Venturi hypothesis” in Poland. Presented data indicate the
protective role of IP against gastric cancer.


VENTURI
Iodide concentration in the stomach
Personal communication from Venturi, March 2007

I think that iodide concentration in stomach is above all in mucinous cells of gastric mucosa and less in
parietal cells, as here reported."  Includes excerpts with pictures from several studies from 1956 -
2006.

Iodine, Helicobacter Pylori, Stomach Cancer & Evolution
Venturi S, Grossi L, Marra GA, Venturi A, Venturi M
The Newsletter of the International Center for Studies and Research in Biomedicine, Luxembourg, Vol.
7, No. 2, April 2003, pp 1-7.

The authors have hypothesized that dietary iodine (I) deficiency or excess are associated with the
development of atrophic gastritis and gastric cancer (GC). They report a short review of their own
work and general literature on this correlation in three fields: (1) epidemiology, where geographical
and temporal correlations between territories with I-deficiency, endemic goitre and high GC-death rate
are reported; (2) iodine and atrophic gastritis correlations, and (3) immunology, where the correlations
between I-deficiency, immune-deficiency and GC are reported. Thyroid cells phylogenetically and
embryologically, derived from primitive I-concentrating gastric cells which, during evolution, migrated
and specialized in uptake and storage of iodine, in order to adapt the organisms from I-rich sea to I-
deficient land. Stomach and thyroid share an important iodide-concentrating ability and an efficient
peroxidase activity, which transfers electrons from iodides to the oxygen of hydrogen peroxide and so
protects the cells from peroxidations. Iodide seems to have an ancestral antioxidant function in all
iodide-concentrating organisms from primitive algae to more recent vertebrates. In Italy, GC is more
frequent in farmers and in I-deficient populations, living in mountainous and hilly areas, than in
fishermen. In the last two decades, Italian decrease of GC seems to be correlated more with the
higher dietary consumption of I-rich fish rather than with consumption of fruit and vegetables, which
indeed has decreased in Italy. In conclusion, iodine deficiency or excess seem to constitute an
important risk factors for atrophic gastritis and GC, both by antioxidant activity and regulating gastric
trophism and by antagonizing the actions of both Helicobacter pylori and of I-inhibitors, such as
nitrates, thiocyanate and salt, well-known risk factors for GC.

Role of iodine in evolution and carcinogenesis of thyroid, breast and stomach.
Venturi S, Donati FM, Venturi A, Venturi M, Grossi L, Guidi A.
Adv Clin Path. 2000 Jan;4(1):11-7. Review.

The authors have hypothesized that dietary iodine (deficiency or excess) is associated with the
development of some gastric and mammary cancers, as it is well-known for thyroid cancer. They
report a short review of their own work and of the general literature on this correlation and on the
antioxidant function of iodide in stomach, breast and thyroid. Thyroid cells phylogenetically derived
from primitive iodide-concentrating gastroenteric cells which, during evolution, migrated and
specialized in uptake and storage of iodine, also in order to adapt the organisms from iodine-rich sea
to iodine-deficient land. Mammary cells also derived from primitive iodide-concentrating ectoderm.
Stomach, breast and thyroid share an important iodide-concentrating ability and an efficient
peroxidase activity, which transfers electrons from iodides to the oxygen of hydrogen peroxide and so
protects the cells from damage caused by lipid peroxidation. The authors suggest that iodide might
have an ancestral antioxidant function in all iodide-concentrating cells from primitive Algae to more
recent Vertebrates. In Italy, gastric cancer is more frequent in farmers and in iodine-deficient
populations, living in mountainous and hilly areas, than in fishermen. In the last two decades, Italian
decrease of gastric cancer seems to be correlated more to the higher dietary consumption of iodine-
rich fish rather than to consumption of fruit and vegetables, which indeed has decreased in Italy.


WAPNIR
Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas
using high density tissue microarrays and conventional sections.
Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, Greco RS, Dohan O,
Carrasco N.
J Clin Endocrinol Metab. 2003 Apr;88(4):1880-8.

Extrathyroidal cancers could potentially be targeted with (131)I, if the Na(+)/I(-) symporter (NIS) were
functional. Using immunohistochemical methods we probed 1278 human samples with anti-NIS
antibody, including 253 thyroid and 169 breast conventional whole tissue sections (CWTS). Four high
density tissue microarrays containing a wide variety of breast lesions, normal tissues, and carcinoma
cores were tested. The results of the normal microarray were corroborated in 50 CWTS. Nineteen of
34 normal tissues, including bladder, colon, endometrium, kidney, prostate, and pancreas, expressed
NIS. Nineteen of 25 carcinomas demonstrated NIS immunopositivity; 55.7% of 479 carcinoma
microarray cores expressed NIS, including prostate (74%), ovary (73%), lung (65%), colon (62.6%),
and endometrium (56%). NIS protein was present in 75% benign thyroid lesions, 73% thyroid cancers,
30% normal-appearing, peritumoral breasts, 88% ductal carcinomas in situ, and 76% invasive breast
carcinoma CWTS. Comparatively, breast microarray cores had lower immunoreactivity. Plasma
membrane immunopositivity was confirmed in thyrocytes, salivary ductal, gastric mucosa, and lactating
mammary cells. In other tissues, immunoreactivity was predominantly intracellular, particularly in
malignant lesions. Thus, NIS is present in many normal epithelial tissues and is predominantly
expressed intracellularly in many carcinomas. Elucidating the regulatory mechanisms that render NIS
functional in extrathyroidal carcinomas may make (131)I therapy feasible.


WU
I-131 total-body scan: localization of disseminated gastric adenocarcinoma. Case report and survey of
the literature.
Wu SY, Kollin J, Coodley E, Lockyer T, Lyons KP, Moran E, Parker LN, Yu AC.
J Nucl Med. 1984 Nov;25(11):1204-9.

This is a case of striking radioiodine and [99mTc]pertechnetate uptake by disseminated nonthyroidal
(gastric) adenocarcinoma. A 65-yr-old man was euthyroid and serum thyroglobulin concentration was
normal at 11 ng/ml. Bone-marrow biopsy showed that the metastatic tumor cells were negative for
thyroglobulin on immunoperoxidase stain and the secretory product was mucicarmine-positive. We
estimate that radioiodine uptake in the normal thyroid gland was less than 10% of total tumor uptake.
At autopsy, the stomach was the site of the primary tumor, which had the same cellular and
histochemical characteristics as the metastatic lesions in bone and liver. It is emphasized that the use
of pertechnetate for screening patients with gastric adenocarcinoma may be clinically useful in the
early detection of metastatic lesions.