Cancers of the gastrointestinal tract remain a substantial cause of death and disease worldwide. In England each year, over 17,000 patients are diagnosed with oesophagus, stomach and liver cancers. Less than 45% of these patients survive 1 year after diagnosis. The cause of these malignancies is still not well understood. Animal studies suggest that nitrate medications (used for angina) could increase gastrointestinal cancer risk. Preclinical evidence suggests that treatments with hormonal effects such as finasteride and hormone replacement therapy (HRT) could protect against gastrointestinal cancer.
This study will determine the association between gastrointestinal cancer risk and use of nitrates, finasteride and HRT. Patients with oesophagus, stomach and liver cancers will be identified from within the CPRD and using cancer registry records. These cancers patients will be matched to individuals attending the same GP practice of similar age and gender who are cancer free. Medication use will be determined in the cancer patients and controls to determine the association between these medications and gastrointestinal cancer risk.
The study could determine that nitrate medications increase gastrointestinal cancer risk; and therefore a careful assessment of the risks and benefits of nitrate use is necessary. It could also show that finasteride or HRT reduces gastrointestinal cancer risk and warrant further study.
Background: Preclinical and epidemiological evidence suggest nitrates could increase gastrointestinal cancer risk and that 5α-reductase inhibitors and HRT could reduce gastrointestinal cancer risk.
Aims: To investigate the associations between nitrates \ 5α-reductase inhibitors \ HRT and gastrointestinal cancer risk.
Methods: A nested case-control study will be conducted within the Clinical Practice Research Datalink (CPRD). In the primary analysis incident gastrointestinal cancer patients will be determined from English cancer registry records (using linkages to the National Cancer Data Repository). The index date in the cases will be their date of cancer diagnosis. Controls will be allocated the index date of their matched case. Exposure to medications will be determined from GP prescription records in the period up to 1 year prior to the index date. Conditional logistic regression will be used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Adjustment for various potential confounders will be conducted. Analyses will be conducted separately by cancer site (oesophageal, gastric and liver).
Potential: The study could determine that nitrate medications are associated with increased gastrointestinal cancer risk; requiring careful risk benefit analysis before use. The study could also identify 5α-reductase inhibitors and HRT as potential chemoprevention agents for these cancers.
Chris Cardwell - Chief Investigator - Queen's University Belfast
Chris Cardwell - Corresponding Applicant - Queen's University Belfast
Jack Murphy - Collaborator - National Cancer Institute ( NCI )
Liam Murray - Collaborator - Queen's University Belfast
Maria Constanza Camargo - Collaborator - National Cancer Institute ( NCI )
Martin Houston - Collaborator - Queen's University Belfast
Minkyo Song - Collaborator - National Cancer Institute ( NCI )
Peter Murchie - Collaborator - University of Aberdeen
Shahinaz Gadalla - Collaborator - National Cancer Institute ( NCI )
Úna McMenamin - Collaborator - Queen's University Belfast
NCRAS Cancer Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation