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Pollutants in pet dogs: a model for environmental links to breast cancer.

Sévère S, Marchand P, Guiffard I, Morio F, Venisseau A, Veyrand B, Le Bizec B, Antignac JP, Abadie J - Springerplus (2015)

Bottom Line: All targeted chemical families were able to be detected in canine samples.We identified pollutants associated with mammary cancer belonging to the dioxin like-PCB family (notably PCB-118, -156, -105, -114) that were already pointed out in human epidemiological studies on breast cancer, and that fit with the fundamental role of the Aryl Hydrocarbon Receptor in the promotion of breast cancer.This study provides a new insight focusing on this discrete but recurrent signature.

View Article: PubMed Central - PubMed

Affiliation: LUNAM University, Nantes-Atlantic College of Veterinary Medicine and Food Sciences (Oniris), USC 1329 INRA Laboratoire d'Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie - CS50707, 44307 Nantes cedex 3, France.

ABSTRACT

Purpose: Invasive breast carcinoma is the most common cancer in women as in non-ovariectomised pet dogs, which are already identified as a valuable spontaneous preclinical model for that disease. Geographical and time trends suggest that environmental factors may play an important role in the etiology and pathogenesis of breast cancer. Persistent organic pollutants (POPs) fit perfectly with these trends and are known to interact with hormonal receptors implicated in breast cancer subtyping. The aim of this innovating study was to evaluate the interest of the companion dog model in assessing chemical exposure and breast cancer associations, in order to identify common etiological features with the human disease in a context of comparative oncology.

Methods: We monitored a hundred of molecules belonging to a large panel of POPs (dioxins, dioxin-like and non dioxin-like polychlorobisphenyls, organochlorine pesticides, brominated flame retardants, perfluorinated alkylated substances) in companion dogs diagnosed for mammary adenocarcinoma (n = 54) and non cancer controls (n = 47).

Results: All targeted chemical families were able to be detected in canine samples. We identified pollutants associated with mammary cancer belonging to the dioxin like-PCB family (notably PCB-118, -156, -105, -114) that were already pointed out in human epidemiological studies on breast cancer, and that fit with the fundamental role of the Aryl Hydrocarbon Receptor in the promotion of breast cancer.

Conclusions: Similarities observed in the spontaneous dog model are very helpful to progress in interpretation of human breast cancer-environment relationships. This study provides a new insight focusing on this discrete but recurrent signature.

No MeSH data available.


Related in: MedlinePlus

Distribution of the measurement points represented by “Box and whisker” plots with a confidence interval of 95% in cancer versus benign tumor cases for PCB-118, PCB-156, PCB-105, PCB-114 and PCB-167.
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Fig3: Distribution of the measurement points represented by “Box and whisker” plots with a confidence interval of 95% in cancer versus benign tumor cases for PCB-118, PCB-156, PCB-105, PCB-114 and PCB-167.

Mentions: Subgroups of pet dogs with similar number of individuals and balanced epidemiological criteria were selected. Hence, 54 breast cancers versus 47 no cancer controls were submitted to non-parametric statistical analyses (Mann-Whitney test). 54 breast cancers versus 30 mammary benign tumors were also compared (Table 1). When pollutants are considered together as a toxic equivalent value or as a total amount of congeners, no significant difference is observed inter-groups. However, when statistical analyses are performed for individual molecules, significant differences inside the dl-PCB family restricted to congeners with a non-coplanar chemical structure (mono-ortho type) are found. Notably, PCB-118 and PCB-156 appear almost twice more concentrated in cancer group (median values) than in control groups and these features seem robust when different populations are compared (Table 3). Significant differences observed for PCB-105, PCB-114 and PCB-167 appear group dependant, understanding that Mann-Whitney test tends to generate false negative results. Excluding PCB-167, this shift towards a higher dl-PCB profile seems not due to atypical individuals amongst cancer group but seems rather to correspond to a continuum, as demonstrated by the repartition of cases or controls as a function of dl-PCB concentrations (Figure 2, Table 4). Lastly we can assume on the one hand that all breast cancer cases are probably not related to this chemical exposure, and on the other hand that some of controls may further develop the disease, which is adequate to explain some overlapping measurement points (Figure 3). When focusing on these congeners regardless the dogs’ pathological status but regarding their physical activity as a hypothetic bias, no significant difference were noticed that could mimetic and explain this profile (Table 5). None of the other 88 molecules among the other five chemical families (dioxins, ndl-PCBs, OCPs, BFRs and PFAS) appeared individually associated to mammary cancer, and multivariate analyses did not reveal any synergistic mixture effect.Table 3


Pollutants in pet dogs: a model for environmental links to breast cancer.

Sévère S, Marchand P, Guiffard I, Morio F, Venisseau A, Veyrand B, Le Bizec B, Antignac JP, Abadie J - Springerplus (2015)

Distribution of the measurement points represented by “Box and whisker” plots with a confidence interval of 95% in cancer versus benign tumor cases for PCB-118, PCB-156, PCB-105, PCB-114 and PCB-167.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310831&req=5

Fig3: Distribution of the measurement points represented by “Box and whisker” plots with a confidence interval of 95% in cancer versus benign tumor cases for PCB-118, PCB-156, PCB-105, PCB-114 and PCB-167.
Mentions: Subgroups of pet dogs with similar number of individuals and balanced epidemiological criteria were selected. Hence, 54 breast cancers versus 47 no cancer controls were submitted to non-parametric statistical analyses (Mann-Whitney test). 54 breast cancers versus 30 mammary benign tumors were also compared (Table 1). When pollutants are considered together as a toxic equivalent value or as a total amount of congeners, no significant difference is observed inter-groups. However, when statistical analyses are performed for individual molecules, significant differences inside the dl-PCB family restricted to congeners with a non-coplanar chemical structure (mono-ortho type) are found. Notably, PCB-118 and PCB-156 appear almost twice more concentrated in cancer group (median values) than in control groups and these features seem robust when different populations are compared (Table 3). Significant differences observed for PCB-105, PCB-114 and PCB-167 appear group dependant, understanding that Mann-Whitney test tends to generate false negative results. Excluding PCB-167, this shift towards a higher dl-PCB profile seems not due to atypical individuals amongst cancer group but seems rather to correspond to a continuum, as demonstrated by the repartition of cases or controls as a function of dl-PCB concentrations (Figure 2, Table 4). Lastly we can assume on the one hand that all breast cancer cases are probably not related to this chemical exposure, and on the other hand that some of controls may further develop the disease, which is adequate to explain some overlapping measurement points (Figure 3). When focusing on these congeners regardless the dogs’ pathological status but regarding their physical activity as a hypothetic bias, no significant difference were noticed that could mimetic and explain this profile (Table 5). None of the other 88 molecules among the other five chemical families (dioxins, ndl-PCBs, OCPs, BFRs and PFAS) appeared individually associated to mammary cancer, and multivariate analyses did not reveal any synergistic mixture effect.Table 3

Bottom Line: All targeted chemical families were able to be detected in canine samples.We identified pollutants associated with mammary cancer belonging to the dioxin like-PCB family (notably PCB-118, -156, -105, -114) that were already pointed out in human epidemiological studies on breast cancer, and that fit with the fundamental role of the Aryl Hydrocarbon Receptor in the promotion of breast cancer.This study provides a new insight focusing on this discrete but recurrent signature.

View Article: PubMed Central - PubMed

Affiliation: LUNAM University, Nantes-Atlantic College of Veterinary Medicine and Food Sciences (Oniris), USC 1329 INRA Laboratoire d'Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie - CS50707, 44307 Nantes cedex 3, France.

ABSTRACT

Purpose: Invasive breast carcinoma is the most common cancer in women as in non-ovariectomised pet dogs, which are already identified as a valuable spontaneous preclinical model for that disease. Geographical and time trends suggest that environmental factors may play an important role in the etiology and pathogenesis of breast cancer. Persistent organic pollutants (POPs) fit perfectly with these trends and are known to interact with hormonal receptors implicated in breast cancer subtyping. The aim of this innovating study was to evaluate the interest of the companion dog model in assessing chemical exposure and breast cancer associations, in order to identify common etiological features with the human disease in a context of comparative oncology.

Methods: We monitored a hundred of molecules belonging to a large panel of POPs (dioxins, dioxin-like and non dioxin-like polychlorobisphenyls, organochlorine pesticides, brominated flame retardants, perfluorinated alkylated substances) in companion dogs diagnosed for mammary adenocarcinoma (n = 54) and non cancer controls (n = 47).

Results: All targeted chemical families were able to be detected in canine samples. We identified pollutants associated with mammary cancer belonging to the dioxin like-PCB family (notably PCB-118, -156, -105, -114) that were already pointed out in human epidemiological studies on breast cancer, and that fit with the fundamental role of the Aryl Hydrocarbon Receptor in the promotion of breast cancer.

Conclusions: Similarities observed in the spontaneous dog model are very helpful to progress in interpretation of human breast cancer-environment relationships. This study provides a new insight focusing on this discrete but recurrent signature.

No MeSH data available.


Related in: MedlinePlus