Page 80 - Read Online

Lonardo. Metab Target Organ Damage 2024;4:7 https://dx.doi.org/10.20517/mtod.2023.56 Page 5 of 7

Household air pollution may also serve as a gender-specific risk factor for liver health in rural areas, as
proven by a large prospective Chinese study disclosing that, compared to men, women with long-term
[30]
exposure to solid fuel combustion were at a higher risk of NAFLD, liver fibrosis, and hepatic cirrhosis .

Pollution and gynecological cancers
The mortality owing to cancer of ovary, uterus, and breast is deemed to be associated with a combination of
factors including air quality, vehicle density, presence of chemical and steel industries, and exposure to
fertilizers .
[31]
Eom et al. found that the risk of uterine cancers was almost 90% higher in industrial areas than in the
control areas . Although incompletely defined, the etiology of uterine cancer is believed to involve
[32]
hormonal derangements, such as perturbed estrogen homeostasis and insulin resistance, that may result
from the action of various air pollutants .
[32]

DNA mutagenesis of the mammary gland cells is directly induced by aromatic hydrocarbons (the prototype
of which is benzo[a]pyrene), which are released by the combustion of coal and petroleum derivatives . A
[33]
recent study suggests that polypropylene microplastics, deemed to be harmless polymers based on Food and
Drug Administration guidelines, instead can enhance the risk of metastatic breast cancer by promoting the
secretion of the inflammatory cytokine IL-6 and the progression of cell cycle in breast cancer cells .
[34]
Finally, some pesticides, which act as endocrine disruptors, affect the hypothalamic-pituitary-ovarian axis
and may trigger ovarian cancers in humans .
[31]
LIMITATIONS AND RESEARCH AGENDA
Investigations addressing the association of NAFLD/MAFLD and gynecological cancers, including the study
by Crudele et al., have failed to assess the impact of multiple confounding factors . These include, among
[16]
others, genetic background and family predisposition to cancer and liver disease, lifestyle habits, exposure to
pollutants, stratification of NAFLD/MAFLD, and variability inherent among different patient populations.

Future studies will have to carefully ascertain whether those genetic polymorphisms of genes, such as
[35]
PNPLA3, which are associated with fibrosing liver disease , also carry an independent impact on the odds
of gynecological cancers.

CONCLUSIONS
Not only NAFLD/MAFLD adult individuals are prone to incident gynecological cancers as discussed above,
but also the prevalence of NAFLD ranges up to 81.3%, with a higher prevalence in breast and gynecological
[36]
cancers . These data, which are consistent with mutual and bi-directional associations, prompt additional
studies investigating all the innumerable clinical and molecular underpinnings of the association between
metabolic dysfunction, hepatic fibrosis, and gynecological cancers.

Prospective confirmation, with adequately sized studies, of the notion that fibrosis in NAFLD/MAFLD,
evaluated with both the diagnostic standard, i.e., liver histology, and with various non-invasive techniques
[37]
is associated with a robust risk of gynecological cancers would bear relevant clinical implications. Indeed,
the scope of medical assistance for these patients would go far beyond liver-related outcomes, to embrace
inter-disciplinary assessment for screening, diagnosis, and management of the various gynecological
cancers. Finally, the intricate pathomechanisms associating liver fibrosis with the risk of gynecological
cancers remain incompletely understood and in need of further investigation.