Dr Marcus Cooke
Dept of Cancer Studies and Molecular Medicine and Genetics
University of Leicester
Leicester, UK
http://www.le.ac.uk/cm/staff/msc5_full.html
http://www.le.ac.uk/cm/gig/escula.html
Project title
Maternal caffeine intake and the presence of chromosomal abnormalities in neonatal blood: implications for future cancer risk (2008/57)
Scientific abstract
Silent chromosomal translocations frequently occur in newborn children. However, the origin of these translocations remains poorly understood. Caffeine, a natural inhibitor of topoisomerase II, induces DNA double strand breaks and may be involved in the production of translocations. Moreover, caffeine enhances error-prone repair by inhibiting ATM kinase, essential for maintaining DNA ends in repair complexes.
The dose of caffeine reaching the foetus depends predominantly upon maternal intake and toxicokinetics. It is proposed that maternal caffeine intake increases the incidence of certain common chromosomal translocations which are observed in both infant and childhood leukaemia. From a mother/baby cohort of 1340 pregnancies this study will screen neonatal DNA from Guthrie cards for common chromosomal translocations. Mothers whose offspring possess translocations in their blood spots will be defined as cases.
It is hoped that the findings from this pilot study will enable a nested case-control evaluation of maternal caffeine intake and genetic polymorphisms in caffeine metabolism to be conducted. Known risk factors, such as folate status, birth weight and oxidative stress would be taken into account. Quantifiable information on maternal caffeine intake, smoking status and alcohol intake would be derived from detailed questionnaires.
Project plain language abstract
Leukaemia is the most common form of childhood cancers (35 % of all childhood malignancies). Chromosomal (DNA) alterations are frequently found in newborn children and have been linked to increased risk of childhood leukaemia. However, the origin of these alterations remains poorly understood. The diet contains compounds, such as caffeine, which promote formation (and persistence) of these chromosomal alterations. There is a wide range of dietary sources of caffeine, and it freely crosses the placenta, leading to the baby’s blood levels being the same as the mother’s. We propose that mother’s caffeine intake increases the incidence of certain common chromosomal translocations which are seen in childhood leukaemia. From an existing mother/baby group of 1340 pregnancies, we propose to screen DNA from the newborns’ heel-prick test for common chromosomal alterations, evaluate mothers’ caffeine intake and ability to metabolise caffeine, using information and specimens already collected. Known risk factors, such as folate status, birth weight and DNA damage will be taken into account, plus other dietary sources of DNA-damaging compounds. This is a unique opportunity to investigate the source of chromosomal alterations during pregnancy which, after further testing, may be a biomarker of newborns with increased susceptibility to future disease
| Institution and location | Degree | Year | Scientific Field |
|---|---|---|---|
| Liverpool Polytechnic, UK | BSc (Hons) MSc |
1991 1994 |
Biomedical Science |
| University of Leicester, UK | PhD | 1998 | Molecular Pathology and Toxicology |
| University of Leicester, UK | MRCPath | 2007 | Free radical biochemistry |
| Royal College of Pathologists, UK | FRCPath | 2008 | Free radical biochemistry |
| 2004–present | Senior Lecturer, Department of Cancer Studies and Molecular Medicine (joint appointment with Department of Genetics), University of Leicester, UK |
| 2002–present | Honorary Research Fellow (Clinical/Surgical), Department of Obstetrics and Gynaecology, University Hospitals of Leicester, NHS Trust, UK |
| 2002–2004 | Lecturer (B), Department of Cancer Studies and Molecular Medicine, University of Leicester, UK (Probationary period accelerated and confirmed in appointment, May 2003) |
| 2001–2001 | Lecturer (B), Division of Chemical Pathology, University of Leicester, UK |
| 1998–2001 | Post-doctoral Research Associate, Oxidative Stress Group, University of Leicester, UK |
| 1996–1998 | Research Assistant, Division of Chemical Pathology, University of Leicester, UK |
| 1991 | Part-time Lecturer in the Biomedical Sciences, Liverpool Polytechnic, UK |
Research interests
Formation and repair of oxidative damage to DNA; role of diet and relationship with cancer risk.
