title: Oxidative Stress Induced Damage to Paternal Genome and Impact of Meditation and Yoga - Can it Reduce Incidence of Childhood Cancer?
abstract: Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also
  affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may
  result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB)
  is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in
  the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who
  consume alcohol in excess and tobacco or who were conceived by assisted conception. The aetiology of childhood
  cancer and increased disease burden in these children is lin ked to oxidative stress (OS) and oxidative DNA
  damage( ODD) in sperm of their fathers. Though several antioxidants are in use to combat oxidative stress, the
  effect of majority of these formulations on DNA is not known. Yoga and meditation cause significant decline in
  OS and ODD and aid in regulating OS levels such that reactive oxygen speues meditated signal transduction, gene
  expression and several other physiological functions are not disrupted. Thus, this study aimed to analyze sperm
  ODD as a possible etiological factor in childhood cancer and role of simple life style interventions like yoga and
  meditation in significantly decreasing seminal oxidative stress and oxidative DNA damage and thereby decreasing
  incidence of childhood cancers. Materials and Methods: A total of 131 fathers of children with RB (non-familial
  sporadic heritable) and 50 controls (fathers of healthy children) were recruited at a tertiary center in India.
  Sperm parameters as per WHO 2010 guidelines and reactive oxygen species (ROS), DNA fragmentation index
  (DFI), 8-hydroxy-2’-deoxy guanosine (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6
  months of intervention. We also examined the compliance with yoga and meditation practice and smoking status
  at each follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels
  were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere
  length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in
  alcoholics (p<0.05) after intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation
  practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3
  months (p<0.05) and 6 months (p<0.05) of practice. Conclusions: Our results suggest that OS and ODD DNA
  may contribute to the development of childhood cancer. This may be due to accumulation of oxidized mutagenic
  base 8OHdG , and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant
  methylation pattern, altered gene expression which affect cell proliferation and survival through activation of
  transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly
  truncatred DNA repair mechanisms all contribute to sperm genome hypermutability and persistant oxidative
  DNA damage. Oxidative stress is also associated with genome wide hypomethylation, telomere shortening and
  mitochondrial dysfunction leading to genome hypermutability and instability. To the best of our knowledge, this
  is the first study to report decline in OS and ODD and improvement in sperm DNA integrity following adoption
  of meditation and yoga based life style modification.This may reduce disease burden in next generation and
  reduce incidence of childhood cancers.
authors.affiliation: Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. rima_dada@rediffmail.com
authors.forename: Dada
authors.initials: D
authors.lastname: Rima
authors.forename: Basant Kumar
authors.initials: BK
authors.lastname: Shiv
authors.forename: Chawla
authors.initials: Ch
authors.lastname: Bhavna
authors.forename: Bisht
authors.initials: B
authors.lastname: Shilpa
authors.forename: Khan
authors.initials: Kh
authors.lastname: Saima
keywords: Childhood cancer; sperm DNA damage; telomeres; DNA gragmentation index