Risks of lymphomas and radon gas - Radoff
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Risks of lymphomas and radon gas

Premise: what is leukemia?

The blood is composed of several corpuscular elements:

  • Erythrocytes, or red blood cells, used to transport oxygen into tissues;
  • Leukocytes, white blood cells that defend the body against infections;
  • Platelets, used to form a coagulative stopper in the event of bleeding.

The three components derive from the same precursors that reside in the bone marrow, from here, once mature, they begin to circulate in the peripheral blood

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Leukemia is a tumor disease: one of the elements that makes up the blood remains blocked in an immature and inefficient stage, or mature but not efficient. This element ("neoplastic clone") replicates out of proportion, and interferes with the entire replicative system of the other components. This implies a lack of functional cells in the blood and an accumulation of these clones. In the most aggressive leukemias the aforesaid inefficient and immature precursors called BLASTI are found in peripheral blood. Blasts can freeze at completely undifferentiated maturation stages, or show signs of maturation towards the myeloid (myeloid leukemia) or lymphoid (lymphatic leukemia) line.

In acute leukemia the number of cancer cells increases faster and the onset of symptoms is early; in chronic leukemia, on the other hand, malignant cells tend to proliferate more slowly. Over time, however, even chronic forms become more aggressive and cause an increase in leukemia cells (immature) within the bloodstream.

What is lymphoma?

Lymphomas such as leukemias are blood cancers, these affect the white blood cell line (of which there are two populations: type B and type T lymphocytes).
Lymphoma (unlike leukemia which mainly originates in the bone marrow where immature cells reside) is a primary solid neoplasm of the lymphatic system, thus involving lymph nodes, lymph-glandular apparatus, T lymphocytes, B lymphocytes and precursors.

Lymphoma arises due to the appearance of genetic mutations in lymphocytes that can acquire the ability to replicate in an uncontrolled way, invading and accumulating in lymph nodes, or in other organs, thus generating a solid tumor mass.

Lymphomas differ in the type of cell being replicated (B or T and their specific cytogenetic markers) and due to the particular mutations that are acquired by tumor cells.
The division is also performed for Hodgkin and Non Hodgkin lymphomas.

A Hodgkin's lymphoma differs from Non-Hodgkin's lymphoma because it presents the Reed-Sternberg cell (= a giant cell characterized by two nuclei instead of just one).

The differential diagnosis between the two types of lymphoma arises with microscopic examination of cells and tissues (histological examination on biopsy), or with molecular analysis, which consists in the study of genetic modifications in the DNA of diseased cells.
As for non-Hodgkin's lymphoma, many subgroups are found.

At this link I reported the most recent WHO 2016 classification on the types of hematological cancers.

Risk of lymphoma linked to the exposure of radon gas in Italy

The aim of the study is to explore the risk of developing type B lymphomas using a case-control study that investigates occupational risk factors, in the provinces of Bari and Taranto, using CAREX (a database to assess exposure to occupational carcinogens. https://www.ttl.fi/en/carex/)

In the same geographical area, 158 cases of lymphomas and 76 controls (recruited in the ophthalmology and orthopedics departments and from the regional registers) were recruited in the provinces of Bari and Taranto.
A blood sample was taken for biological studies on blood and the occupational exposure and work history were investigated with retrospective interviews structured according to a questionnaire validated by the "Epilymph" project (includes socio-demographic factors, education, family history and personal, residential history, work history, diet, smoking, physical activity, reproductive history.) The Italian Cancer Registry Association reports that between 2007 and 2010 the incidence of haematological tumors turned out to be lower in Southern Italy than in the Northern Italy. The authors suppose that this could be due to a lower exposure to environmental carcinogens, to smoking and to a more prevalence of protective factors such as the Mediterranean diet and the younger age of the first pregnancy. Although the risk of developing tumors is lower, southern agricultural men report an increased risk of certain types of hematological cancers, particularly a study by Rieutort et al. found that Non-Hodgkin's Lymphoma increased in both agricultural and industrial workers in the pesticide or solvent sector. The analysis focused on exposure to pesticides (Captafol and Paraquat) and on Radon exposure, consequently calculating the odds ratio (prevalence ratio between exposed and unexposed subjects and between cases, ie patients, that between the controls, that is among the healthy) for the different classes of lymphomas based on the cumulative exposure to the test substance.

With regard to univariate analyzes, the risk of developing lymphoma based on work activity was significant only for workers in the agricultural sector based on the data obtained.

The risk of developing lymphoma based on exposures to:

  • 22 chemicals, most of which were not statistically significant. -10 physical factors none of which are significant (including exposure to medium-high amounts of radon reporting an OR 3.28 with an IC 0.92-11.71)
  • Heavy metals (no significant data found)
  • Drugs (no significant data found)
  • Smoking (confirmed not to be a significant risk factor for lymphomas)
  • Pesticides (in particular Parquat and Captafol reported a positive OR)
  • Familiarity with 4 types of tumors (no significant data are found, only a positive OR for breast cancer)

Multivariate analyzes focused in particular on exposure to the aforementioned pesticides (captafol and paraquat) and to radon, in subjects who were exposed to agricultural or industrial exposure.
The data show an increased risk of lymphomas in general due to exposure to Captafol, in particular non-Hodgkin's lymphoma.

Similar data were found for Paraquat and Radon. The latter specifically reported an OR = 9.5 for exposures at medium-high levels; IC 1.2-76.8 for the risk of developing lymphomas in general and an OR = 8.8; IC 1.2-71.4 for development of non-hodgkin type lymphomas. Thus letting us understand a positive correlation between the two factors.

According to the data, all categories of non-hodgkin lymphoma are positively associated with exposure to medium-high levels of radon: DLBCL (widespread B-cell lymphoma) (OR: 13.7; IC 1.3-143.0); FL (follicular lymphoma) (OR = 12.7; IC 1.2-137.2); SBCL (single-cell B lymphoma) (OR = 64.4; IC 2.1-1956,6); MM (multiple myeloma) (OR = 106.1; IC 1.3-8620); CLL (chronic lymphocytic leukemia) (OR = 10.8; IC 0.9-130.1).

The last analysis shows an association between workers in the agricultural sector and non-hodgkin lymphomas of the DLBCL and MM type.
The authors in the discussion of the article report how this data is confirmed by other studies. They explain how according to other studies the fungicide Captafol (which the IARC classifies as probably carcinogenic to humans) and the herbicide Paraquat have been related to Non-Hodgkin's Lymphomas, and that the use of these products is increased in Puglia; they follow explaining the theories about the mechanism of action of these products in the DNA mutation.

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As far as the Radon is concerned, the authors explain that the subjects most exposed are the agric oil workers, the food and drink production workers, the electricity workers. Radon can be easily inhaled as a gas, but its decay products are solid and settle. The evaluation of radon levels in Puglia has shown that only in particular regions does its concentration exceed 300 Bq / m3, but for farmers the exposure is constant over time.
They also cite studies that suggest an increased incidence of DLBCL lymphoma among children exposed to high levels of residential radon and studies on miners from Uranium quarries that have reported an increase in the incidence of chronic lymphocytic leukemia and Hodgkin's lymphomas, and an increase of mortality due to non-hodgkin type lymphomas due to the increase in gamma-ray doses.

The authors conclude by explaining how this is a preliminary study but that reveals how agricultural workers exposed to Captafol, Paraquat and Radon can go on to develop different types of lymphoma, in particular DLBCL (large B cell lymphoma).

Dott.ssa Giulia Gabrielli