Tobacco smoking
Smoking is one of the best-established carcinogenic hazards. Of note is
that previous studies on childhood cancer epidemiology have mostly shown
null associations between maternal smoking and risk of childhood cancer,
which is in line with the results of the present umbrella review. By
contrast, paternal smoking during pregnancy has been more consistently
reported as potential risk factor of childhood cancer, especially ALL,
which was also supported by the herein results; the magnitude of this
effect was calculated at 1.20 summary random effects estimate. Our study
also found suggestive evidence for paternal ever smoking, even before
pregnancy in relation to childhood leukemia. IARC considered the
evidence from different studies as sufficient to suggest a causal link
between paternal smoking and childhood cancers. Exposure to mutagenic
polycyclic aromatic compounds from tobacco smoke can increase the
formation of DNA adducts in sperm. Smoking also induces the generation
of reactive oxygen species and reduces levels of antioxidant cellular
defenses, thus contributing to oxidative stress and DNA damage.
Oxidative DNA damage is not randomly distributed in mature human
spermatozoa but occurs preferentially in unpackaged, protein-free
regions of the genome in close proximity to the nuclear membrane, which
are especially vulnerable to oxidative stress. Overall, tobacco smoke
may cause genetic changes through the germline that may make children
more susceptible to developing cancer[NO_PRINTED_FORM]. Indeed,
paternal smoking may contribute up to 1.3 million extra cases of
aneuploid pregnancies per generation due to smoking-induced de
novo germline mutations transmitted from fathers to offspring. In
addition, recent epigenome-wide association studies (EWASs) suggest that
tobacco affects the genomic DNA methylation profiles. Smoking-related
cytosine-phosphate-guanine (CpG) sites have been identified in various
genes, such as AHRR , F2RL3 and GPR15 , which could
be used as predictors of smoking-related health risks. Tobacco-related
products may induce specific differences in the spermatozoal microRNA
content, which subsequently mediate pathways vital for healthy sperm and
normal embryo development, particularly cell death and apoptosis.
Smoking may also alter genomic imprinting due to DNA hypomethylation and
reduce sperm cytosine methyl transferase messenger RNA levels, which
may, in turn, lead to the expression of normally silent paternal
alleles.