Pesticide exposure and lymphohaematopoietic cancers: a case-control study in an agricultural region (Larissa, Thessaly, Greece)

<p>Abstract</p> <p>Background</p> <p>The causality of lymphohaematopoietic cancers (LHC) is multifactorial and studies investigating the association between chemical exposure and LHC have produced variable results. The aim of this study was to investigate the relationships between exposure to pesticides and LHC in an agricultural region of Greece.</p> <p>Methods</p> <p>A structured questionnaire was employed in a hospital-based case control study to gather information on demographics, occupation, exposure to pesticides, agricultural practices, family and medical history and smoking. To control for confounders, backward conditional and multinomial logistic regression analyses were used. To assess the dose-response relationship between exposure and disease, the chi-square test for trend was used.</p> <p>Results</p> <p>Three hundred and fifty-four (354) histologically confirmed LHC cases diagnosed from 2004 to 2006 and 455 sex- and age-matched controls were included in the study. Pesticide exposure was associated with total LHC cases (OR 1.46, 95% CI 1.05-2.04), myelodysplastic syndrome (MDS) (OR 1.87, 95% CI 1.00-3.51) and leukaemia (OR 2.14, 95% CI 1.09-4.20). A dose-response pattern was observed for total LHC cases (P = 0.004), MDS (P = 0.024) and leukaemia (P = 0.002). Pesticide exposure was independently associated with total LHC cases (OR 1.41, 95% CI 1.00 - 2.00) and leukaemia (OR 2.05, 95% CI 1.02-4.12) after controlling for age, smoking and family history (cancers, LHC and immunological disorders). Smoking during application of pesticides was strongly associated with total LHC cases (OR 3.29, 95% CI 1.81-5.98), MDS (OR 3.67, 95% CI 1.18-12.11), leukaemia (OR 10.15, 95% CI 2.15-65.69) and lymphoma (OR 2.72, 95% CI 1.02-8.00). This association was even stronger for total LHC cases (OR 18.18, 95% CI 2.38-381.17) when eating simultaneously with pesticide application.</p> <p>Conclusions</p> <p>Lymphohaematopoietic cancers were associated with pesticide exposure after controlling for confounders. Smoking and eating during pesticide application were identified as modifying factors increasing the risk for LHC. The poor pesticide work practices identified during this study underline the need for educational campaigns for farmers.</p

Assessment of risk factors (plant protection products) for the development of lymphohaematopoietic cancers in the agricultural region of Thessaly, Greece

The causality of lymphohaematopoietic cancers (LHC) is multifactorial and studies investigating the association between chemical exposure and LHC have produced variable results. The aim of this study was to investigate the relationships between exposure to pesticides and LHC and the association between Paraoxonase 1 (PON1) gene polymorphisms (M55L and Q192R) and LHC in an agricultural region of Greece. A structured questionnaire was employed in a hospital-based case control study to gather information on demographics, occupation, exposure to pesticides, agricultural practices, family and medical history and smoking. To control for confounders, backward conditional and multinomial logistic regression analyses were used. To assess the dose-response relationship between exposure and disease, the chi-square test for trend was used. Genotyping of cases and controls was performed by using standard laboratory methods. Three hundred and fifty-four (354) histologically confirmed LHC cases diagnosed from 2004 to 2006 and 455 sex- and age-matched controls were included in the study. Pesticide exposure was associated with total LHC cases (OR 1.46), myelodysplastic syndrome (MDS) (OR 1.87) and leukaemia (OR 2.14) with a dose-response pattern. Pesticide exposure was independently associated with total LHC cases (OR 1.41) and leukaemia (OR 2.05) after controlling for age, smoking and family history (cancers, LHC and immunological disorders). Smoking during application of pesticides was strongly associated with total LHC cases (OR 3.29), MDS (OR 3.67), leukaemia (OR 10.15) and lymphoma (OR 2.72). This association was even stronger for total LHC cases (OR 18.18) when eating simultaneously with pesticide application. The genotyping included 316 cases 351 controls. The QQ genotype was associated with increased risk of LHC (OR 1.94). The QQ genotype in the recessive model was independently associated with LHC (OR 1.92), leukaemia (OR 1.99), lymphoma (OR 2.17) and plasmacell disease (OR 1.92) even after controlling for the confounders. We found no association between M55L polymorphism and LHC. Lymphohaematopoietic cancers were associated with pesticide exposure after controlling for confounders. Smoking and eating during pesticide application were identified as modifying factors increasing the risk for LHC. Carriers of the 192Q allele may have an increased risk for LHC. The results encourage further investigation on the PON1 polymorphisms and their importance on the individual’s susceptibility especially when exposure to pesticides occurs. The poor pesticide work practices identified during this study underline the need for educational campaigns for farmers.Η Θεσσαλία είναι η δεύτερη περιφέρεια σε αγροτική παραγωγή στην Ελλάδα. Η χρήση φυτοπροστατευτικών προϊόντων (φππ) έχει συσχετιστεί με την ανάπτυξη καρκίνου του αίματος. Η γενετική προδιάθεση επηρεάζει την πιθανότητα εμφάνισης της νόσου. Οι κυριότεροι στόχοι της μελέτης είναι η ποσοτικοποίηση της έκθεσης, η διερεύνηση των πρακτικών εφαρμογής των φππ καθώς και η διερεύνηση των πολυμορφισμών της ΡΟΝ1 (L55M και Q192R). Πρόκειται για μια μελέτη πασχόντων και μαρτύρων στους οποίους χρησιμοποιήθηκε προτυποιημένο ερωτηματολόγιο που περιελάμβανε δημογραφικά στοιχεία, επάγγελμα, έκθεση σε φππ, πρακτικές εφαρμογής τους, οικογενειακό και ατομικό ιατρικό ιστορικό και κάπνισμα. Λήφθηκαν δείγματα αίματος για γονιδιακή ανάλυση. Συγκεντρώθηκαν 354 ιστολογικά επιβεβαιωμένοι πάσχοντες και 455 μάρτυρες. Βρέθηκε ότι η έκθεση σε φππ αυξάνει τον κίνδυνο ανάπτυξης αιματολογικών νεοπλασιών (OR 1,46), μυελοδυσπλαστικού συνδρόμου (ΜΔΣ) (OR 1,87) και λευχαιμίας (OR 2,14) και μάλιστα με σχέση δοσοεξάρτησης. Μετά τον έλεγχο των ακόλουθων συγχυτικών παραγόντων: οικογενειακό ιστορικό (για νεοπλασίες όλων των τύπων, αιματολογικές νεοπλασίες, ανοσολογικά νοσήματα), ηλικία και κάπνισμα, βρέθηκε ότι η έκθεση σε φππ αποτελεί ανεξάρτητο παράγοντα κινδύνου για την ανάπτυξη αιματολογικών νεοπλασιών (OR 1,41) και συγκεκριμένα λευχαιμίας (OR 2,05). Το κάπνισμα κατά τη διάρκεια της εργασίας βρέθηκε ότι έχει ισχυρή συσχέτιση με την ανάπτυξη αιματολογικών νεοπλασιών (OR 3,29), ΜΔΣ (OR 3,67), λευχαιμίας (OR 10,15) και λεμφώματος (OR 2,72). Αυτή η συσχέτιση ήταν ακόμη μεγαλύτερη όταν ταυτόχρονα συνδυάζεται και με την κατανάλωση φαγητού κατά την εργασία (OR 18,18). Τα κριτήρια για να συμπεριληφθούν στην εργαστηριακή ανάλυση για τη γονοτύπωση της ΡΟΝ1 πληρούσαν 316 δείγματα πασχόντων και 351 δείγματα μαρτύρων. Ο γονότυπος QQ συσχετίστηκε με αυξημένο κίνδυνο εμφάνισης αιματολογικών νεοπλασιών (OR 1,94). Μετά τον έλεγχο των παραπάνω συγχυτικών παραγόντων βρέθηκε ότι ο γονότυπος QQ αποτελεί ανεξάρτητο παράγοντα κινδύνου για την ανάπτυξη αιματολογικών νεοπλασιών (OR 1,92), λευχαιμίας (OR 1,99), λεμφώματος (OR 2,17) και πλασματοκυτταρικών δυσκρασιών (OR 1,92). Δεν βρέθηκε στατιστικώς σημαντική συσχέτιση για τον πολυμορφισμό M55L της ΡΟΝ1. Η παρούσα μελέτη προσπαθεί να ποσοτικοποιήσει την συνολική έκθεση για όλη τη διάρκεια της ζωής των συμμετεχόντων, ενσωματώνοντας μεγέθη όπως η συχνότητα, η διάρκεια και η ένταση της έκθεσης. Η έκθεση σε φππ, το κάπνισμα και το φαγητό κατά τη διάρκεια της αγροτικής εργασίας καθώς και ο γονότυπος QQ βρέθηκε ότι συνδέονται με την ανάπτυξη αιματολογικών νεοπλασιών. Η αγροτική υγεία είναι ανάγκη να αποτελέσει πεδίο προτεραιότητας για τις υπηρεσίες πρωτοβάθμιας φροντίδας υγείας αλλά κάτι τέτοιο προϋποθέτει την ύπαρξη οργανωμένων υποδομών καθώς και κατάλληλη εκπαίδευση του αγροτικού πληθυσμού

Relationship between the paraoxonase 1 (PON1) M55L and Q192R polymorphisms and lymphohaematopoietic cancers in a Greek agricultural population

The aim of this study was to investigate the association between Paraoxonase 1 (PON1) gene polymorphisms (M55L and Q192R) and lymphohaematopoietic cancers (LHC) in an agricultural region of Greece. A hospital-based case-control study was conducted. A structured questionnaire including information on demographics, residence, occupation, agricultural practices, pesticide exposure, family history, smoking, alcohol consumption and medical history, was used. Genotyping of 316 cases of LHC and 351 healthy controls by using standard laboratory methods was performed. To control for confounders, Binary and Multinomial Logistic Regression analyses were used. Possession of QQ genotype or presence of the Q allele were associated with increased risk of developing LHC (OR 1.94, 95% Cl 1.42-2.66 and OR 1.72, 95% Cl 1.33-2.23 respectively). The QQ genotype in the recessive model was independently associated with LHC (OR 1.92, 95% Cl 1.40-2.65), leukaemia (OR 1.99, 95% CI 1.13-3.49), lymphoma (OR 2.17, 95% CI 1.21-3.90) and plasmacell disease (OR 1.92, 95% Cl 1.40-2.65) even after controlling for age, sex, pesticide exposure, smoking and family history (cancers, LHC and immunological disorders) as confounders. Possession of QQ genotype was found to have a stronger association with LHC in the high and medium pesticide exposed groups(OR 2.15, 95% CI 1.35-3.40, P-value 0.001 and OR 2.25,95% CI 1.21-4.19, P-value 0.010 respectively), compared with the Low/No exposed group where the association was not statistically significant (OR 1.51,95% CI 0.76-3.00, P-value 0.224). We found no association between M55L polymorphism and LHC. PON1 polymorphisms may influence the risk for LHC in our agricultural area. The results encourage further investigation on the PON1 polymorphisms and their importance on the individual's susceptibility especially when exposure to pesticides occurs. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Mechanism underlying the effect of long-term exposure to low dose of pesticides on DNA integrity

Pesticides, including herbicides, insecticides and fungicides, are widely used in intensive agriculture. Recently, the long-term effects of pesticide exposure were found to be associated with many diseases. In this study, we evaluated the long-term effect of low-level exposure to a mixture of pesticides on DNA damage response (DDR) in relation to individual detoxifying variability. A residential population chronically exposed to pesticides was enrolled, biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192 Q/R polymorphism and DDR were evaluated at three different periods of pesticide exposure. OGG1-dependent DNA repair activity was decreased in relation to pesticide exposure. The increase of DNA lesions and pesticide levels in the intensive pesticide-spraying period was independent on PON-1 activity. Next, human bronchial epithelial and neuronal cells were used as a model for in vitro evaluation of the mechanistic effect of pesticides. Pesticides induced mitochondrial dysfunction leading to ROS formation. ROS from mitochondria induced DNA damage, which in turn induced OGG1-dependent DNA repair activity through 8-oxoguanine DNA glycosylase 1 (OGG1) expression and activation. Even though OGG1 was overexpressed, an inhibition of its activity, associated with DNA lesion accumulation, was found at prolonged pesticide-exposure. A post-translational regulation of OGG1 by pesticide may be postulated. Taken together, long-term exposure to low-levels of pesticides affects DDR resulting in accumulation of DNA lesions that eventually may lead to cancer or neurological disorders