Associations of gene expression in blood with BMI and weight changes among women in the Norwegian Women and Cancer postgenome cohort.

OBJECTIVE: This study aimed to evaluate associations between blood gene expression profiles and (1) current BMI and (2) past weight changes (WCs) among women who had never been diagnosed with cancer in the Norwegian Women and Cancer (NOWAC) postgenome cohort. METHODS: This cross-sectional study (N = 1694) used gene expression profiles and information from three questionnaires: Q1 (baseline), Q2 (follow-up), and Q3 (blood collection). The authors performed gene-wise linear regression models to identify differentially expressed genes (DEGs) and functional enrichment analyses to identify their biological functions. RESULTS: When assessing BMIQ3 , the study observed 2394, 769, and 768 DEGs for the obesity-versus-normal weight, obesity-versus-overweight, and overweight-versus-normal weight comparisons, respectively. Up to 169 DEGs were observed when investigating WCQ3-Q1 (mean = 7 years, range = 5.5-14 years) and WCQ3-Q2 (mean = 1 year, range = <1 month-9 years) in interaction models with BMI categories, of which 1 to 169 genes were associated with WCs and 0 to 9 were associated with interaction effects of BMI and WCs. Biological functions of BMI-associated DEGs were linked to metabolism, erythrocytes, oxidative stress, and immune processes, whereas WC-associated DEGs were linked to signal transduction. CONCLUSIONS: Many BMI-associated but few WC-associated DEGs were identified in the blood of women in Norway. The biological functions of BMI-associated DEGs likely reflect systemic impacts of obesity, especially blood reticulocyte-erythrocyte ratio shifts.

Gene expression in blood reflects smoking exposure among cancer-free women in the Norwegian Women and Cancer (NOWAC) postgenome cohort.

Active smoking has been linked to modulated gene expression in blood. However, there is a need for a more thorough understanding of how quantitative measures of smoking exposure relate to differentially expressed genes (DEGs) in whole-blood among ever smokers. This study analysed microarray-based gene expression profiles from whole-blood samples according to smoking status and quantitative measures of smoking exposure among cancer-free women (n = 1708) in the Norwegian Women and Cancer postgenome cohort. When compared with never smokers and former smokers, current smokers had 911 and 1082 DEGs, respectively and their biological functions could indicate systemic impacts of smoking. LRRN3 was associated with smoking status with the lowest FDR-adjusted p-value. When never smokers and all former smokers were compared, no DEGs were observed, but LRRN3 was differentially expressed when never smokers were compared with former smokers who quit smoking ≤ 10 years ago. Further, LRRN3 was positively associated with smoking intensity, pack-years, and comprehensive smoking index score among current smokers; and negatively associated with time since cessation among former smokers. Consequently, LRRN3 expression in whole-blood is a molecular signal of smoking exposure that could supplant self-reported smoking data in further research targeting blood-based markers related to the health effects of smoking.