Tobacco Use Increases Oxidative DNA Damage in Sperm - Possible Etiology of Childhood Cancer

Abstract

Background: Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing). Materials and Methods: We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models. Results: There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01). Conclusions: This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA.

Oxidative Stress and Polymorphism in MTHFR SNPs (677 and 1298) in Paternal Sperm DNA is Associated with an Increased Risk of Retinoblastoma in Their Children: A Case–Control Study

“…The cut-off values for seminal oxidative stress biomarkers, that is, ROS, DFI, and 8-OH2dG, were taken from the study previously published by Kumar et al (2016). 20 The standard semen parameters such as sperm motility, count, and morphology were found to be comparable in fathers of RB patients and healthy controls.…”

“…This suggested that oxidative stress and oxidative DNA damage may serve as a possible etiological factor for the causation of sporadic nonfamilial heritable RB. 20 Therefore, we may conclude that factors like advanced paternal age and poor lifestyle habits may contribute to the generation of oxidative stress in the male germline. This, together with MTHFR polymorphisms, causes aberrant DNA methylation patterns in the sperm DNA and further increases the oxidative stress by decreasing the glutathione production.…”

Sperm DNA fragmentation index does not correlate with blastocyst aneuploidy or morphological grading

“…DNA Fragmentation Index was performed at the judgment of the attending physician especially in cases of risk factors for abnormal DFI (ex. Smoking [21]) and abnormal semen analysis according to WHO criteria [22]. …”

Sperm DNA fragmentation in donors and normozoospermic patients attending for a first spermiogram: Static and dynamic assessment

“…Over the past years, numerous studies have emphasised on significant associations between poor sperm DNA integrity and impaired fertilisation (Jin et al., ), deteriorated implantation and early embryogenesis (Simon et al., ), miscarriages (Coughlan et al., ), birth defects and childhood cancers (Kumar, Chawla, Bisht, Yadav, & Dada, ). In general, most of these conclusions are derived from a static sperm DNA damage assessment obtained after ejaculation in fertile as well as infertile men.…”