Dr Paul Brennan
Group of Genetic Epidemiology, Section of Genetics
International Agency for Research on Cancer [IARC-WHO], The World Health Organization
Lyon, France
Project 1 title
Evaluating the protective effect of folate against lung cancer in a large European prospective study (2007/16)
Project 2 title
Evaluating the effects of B- and D-vitamins in renal cell cancer in two large European prospective studies (R2010/254).
Scientific abstract 1
Given the high risk of lung cancer that remains among former smokers identification of chemopreventive agents for these cancers is clearly important. Numerous studies have reported that fruits and vegetables are protective against lung cancer, and folate has been suggested as one of the chemopreventive compounds responsible for such a protective effect. Pilot data for this association was generated by observing that in a large case-control study of over 2000 lung cancer cases and comparable controls, a methylenetetrahydrofolate (MTHFR) gene variant that codes for low circulating folate levels increased the risk of lung cancer, (OR=1.3, 95%CI 1.1-1.9), with the risk being particularly important for those with low dietary levels of folate (OR=1.8, 95%CI 1.3-2.7). In order to provide a comprehensive and valid test of this hypothesis based on prospectively collected data, a nested case-control analysis within the EPIC cohort study of 500,000 European subjects will be conducted. In particular, the study will identify 1600 lung cancer cases, and 3200 matched controls, and (i) compare pre-diagnostic folate serum levels between those who develop lung cancer and those who do not, (ii) assess reported dietary folate, and (iii) genotype for the MTHFR variant that is known to influence folate levels.
Scientific abstract 2
Background: This is a renewal of our WCRF funded project that focused on B-vitamins and lung cancer (2007/16). In this recently completed analysis, based on prospectively collected blood samples within the EPIC cohort, we identified a strong independent association between lung cancer and several serum biomarkers including Vitamin B6, methionine and folate.
This study will now be extended to renal cell carcinoma (RCC) including the following innovative aspects:
- a parallel investigation of serum vitamin D and RCC
- inclusion of repeat samples to allow correction for regression dilution
- evaluation of these biomarkers on cancer survivorship.
Objectives: Our objectives are to accurately measure circulating levels of vitamin B2, B6, B12, methionine, folate, and homocysteine in pre-diagnostic blood samples from RCC cases and comparable controls. We will also measure in the same laboratory circulating vitamin D levels among cases and controls, taking advantage of the large cost saving that this will involve.
We will also incorporate an analysis of 'regression dilution' that corrects for day-today variation in biomarkers, and will assess whether any of the measured biomarkers correlate with survival after RCC diagnosis.
Settings and Methods: The study population will include 600 RCC cases and 1,200 controls from two large European prospective cohorts, the EPIC cohort study (approximately 400 cases and 800 controls), and the HUNT2/Tromsø cohort study (approximately 200 cases and 400 controls). All cases have developed RCC after recruitment to the study and provision of a blood sample. Two matched controls will be selected for each case. For 200 controls we will include a repeat blood sample. 500 µL of serum from all study participants will be analysed by the BEVITAL laboratory and measurements will be provided for a total of 40 vitamins, metabolites and enzymes related to one-carbon metabolism, as well as vitamin D. Survival information will be collected on all 600 cases.
Impact: This study will provide essential population based evidence on the role of both B-vitamins and also vitamin D in RCC, and will extend our knowledge for these vitamins and their potential chemo-preventative role in cancer in general. Specifically, we will test whether, similar to lung cancer, there are independent effects for vitamin B6, methionine and folate, and may provide important biomarkers for RCC risk. In the process, we will also increase our knowledge of the nutritional epidemiology of RCC, which is currently very limited. A role for vitamin D will strengthen the evidence for a protective effect of this biomarker, and increase the need for large randomized trials.
Project 1 plain language abstract
A strong and consistent increased risk has been observed for lung cancer among individuals who have diets deficient in fruits and vegetables. A primary hypothesis for this is that such diets are particularly deficient in folate, and that folate deficiency may increase the risk of lung cancer. We have generated pilot data to this effect by observing that in a large series of 2000 lung cancer cases and 2000 comparable controls, a gene variants in the methylenetetrahydrofolate (MTHFR) gene that codes for low circulating folate levels increased the risk of lung cancer by 30%, with the risk being particularly important for those with low dietary levels of folate. Such findings have important implications for the chemoprevention of lung cancer. In order to provide a comprehensive and valid test of this hypothesis based on prospectively collected data, we will conduct a study within a large population cohort of 500,000 European people. In particular, we will compare 1600 individuals who developed lung cancer after they entered the study to 3200 individuals who did not develop lung cancer and (i) compare pre-diagnostic folate serum levels, (ii) assess reported dietary folate, and (iii) genotype for the MTHFR variant known to reduce folate levels.
Project 2 plain language abstract
Background: In a recent WCRF funded project that focused on lung cancer (2007/16), we showed within a large cohort study that several B-vitamins, in particular folate, vitamin B6 and a related compound called methionine, had a strong protective effect for lung cancer. These results were based on blood samples taken several years before diagnosis (on average 6 years) and were the same in smokers and never-smokers. We will now investigate whether similar associations exist for kidney cancer (also know as renal cell carcinoma), a cancer site for which we have little knowledge regarding the role of diet. This study will including the following additional innovative aspects: (i) we will also investigate whether high levels of serum vitamin D are protective against kidney cancer, (ii) we will measure a subgroup of subjects twice, allowing us to include in the analysis the extent to which blood measures vary, and (iii) we will evaluate whether any of these biomarkers have a role in cancer survivorship.
Aims and Goals: Our main objectives are to accurately measure the blood levels of six B vitamins and related biomarkers: vitamin B2, B6, B12, methionine, folate, and homocysteine. This will be measured in blood samples taken before disease onset among 600 kidney cancer cases, and a group of 1200 comparable controls. We will also measure in the same laboratory circulating vitamin D levels among all cases and controls, taking advantage of the large cost saving that this will involve. We will correct all our results for day-today variation in these biomarkers, and will assess whether any of them correlate with survival after kidney cancer diagnosis.
How it will be done: 600 kidney cancer cases and 1200 comparable controls will be identified from two large European cohort studies: (i) the EPIC cohort comprising blood and questionnaire data on 385,747 adults from 10 European countries, and the HUNT2/Tromsø study comprising over 90,000 individuals from Trondheim and Tromsø in Norway. Approximately two thirds of the cases will come from EPIC and one third from HUNT2/Tromsø. For an additional 200 controls we will also have a repeat blood sample collected at a later period in time. Serum from all study participants will be sent to the BEVITAL laboratory in Bergen, Norway, and measurements will be provided for a total of 40 vitamins, metabolites and enzymes related to B-vitamins as well as vitamin D. The cause of death after cancer diagnosis will be collected on all 600 cases.
Potential Impact: The study will provide important evidence on the role of both B-vitamins and also vitamin D in kidney cancer, and will extend our knowledge for these vitamins and their potential chemo-preventative role in cancer in general. Specifically, we will test whether, similar to lung cancer, there are independent effects for multiple B-vitamins (in particular vitamin B6, methionine and folate), and investigate whether combinations of these may provide important biomarkers for RCC risk. In the process, we will also increase our knowledge of the nutritional epidemiology of RCC, which is currently very limited, A role for vitamin D will strengthen the evidence for a protective effect of this biomarker, and increase the need for large randomized trials.
| Institution and location | Degree | Year | Scientific Field |
|---|---|---|---|
University of Leicester , UK |
BSc |
1988 |
Mathematics (Hons) |
University of Leicester, UK |
MSc |
1989 |
Medical Statistics |
Royal College Physicians, UK |
Diploma |
1994 |
Epidemiology |
University of Manchester, UK |
PhD |
1995 |
Genetic Epidemiology |
| 2009-Present | Head, Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer [IARC-WHO], The World Health Organization, Lyon, France |
| 2005-2009 | Head, Group of Genetic Epidemiology, IARC, Lyon, France |
| 1997-2004 | Scientist in the Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer (IARC), Lyon, France |
| 1989-1996 | Lecturer in Epidemiology and Medical Statistics, ARC Epidemiology Research Unit, University of Manchester Medical School, UK |
Research interests
Epidemiology; genetics.
