The NOWAC postgenome cohort: A unique design to develop blood-derived transcriptomic profiles as a mean to biomonitor defined exposure and its effect on cancer incidence
Authors: Vanessa Dumeaux, Anne-Lise Borresen-Dale, Eiliv Lund
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2979 

The overall project aim is to investigate in a prospective design with repeated measurement the promising results using peripheral blood for transcriptome analyses to study gene-environment interactions related to disease state (e.g. breast cancer). At start, we aim to develop blood-derived transcriptomic profiles as means to biomonitor exposure measured both by questionnaire and plasma levels.

The NOWAC postgenome cohort consists of approximately 50,000 women born 1943-57. The women are part of the NOWAC study (1) consisting of 170,000 women aged 30-70 years at recruitment during 1991-2006 who filled in an 8-page questionnaire on diet and lifestyle. The women born 1943-57 were asked to give 2 blood samples for extraction of DNA, RNA and plasma measurements and to fill in an additional 2-page questionnaire with information on current use of medications, smoking, alcohol, height and weight. Information on cancer cases within NOWAC cohort are sought by linkage to the Norwegian Cancer Register based on the unique person number. All women born between 1943 and 1957 participating in the cohort that are diagnosed with a breast cancer are asked to give an informed consent to collect blood samples and fresh tumor tissue at the time of diagnosis. With an incidence rate of breast cancer in 2004 in the actual age groups of 274/100.000 per year and the participation of the 11th largest hospital in Norway, collection of about 100 biopsies/year is expected. In parallel, we will collect blood samples from age-matched control.

In our study, measurements of biomarkers in plasma (i.e. hormones, organic pollutants, vitamin D, fatty acids) will be compared to the questionnaire data as a cross-validation in about 400 women. The estimated exposures from the questionnaires or measured biomarkers will be analysed as predictors for expression patterns in whole blood. The statistical power should be sufficient for stratified analyses or for looking at combined exposures. In parallel, studies on the importance of different single nucleotide polymorphisms on the gene expression patterns will be performed.

This study will partly be an association study of important exposures for cancer that will at the same time function as validation of questionnaire used in prospective etiological studies. In addition, micro-array analyses will give information on regulated metabolic pathways associated to exposure and hence the gene-exposure interactions in relation to disease risk can be evaluated. We are in position to make an important contribution to future array analyses due to the population-based samples of our cohort and the potential strong statistical power that the size of this biobank offers.

(1) Lund E et al. External validity in a population-based national prospective study--the Norwegian Women and Cancer Study (NOWAC) Cancer Causes Control 2003;14:1001-1008