Circulating Biomarker Score for Visceral Fat and Risks of Incident Colorectal and Postmenopausal Breast Cancer: The Multiethnic Cohort Adiposity Phenotype Study
Loı̈c Le Marchand, Lynne R. Wilkens, Ann M. Castelfranco, Kristine R. Monroe, Bruce S. Kristal, Iona Cheng, Gertraud Maskarinec, Meredith A.J. Hullar, Johanna W. Lampe, John Shepherd, Adrian A. Franke, Thomas Ernst, Unhee Lim
Abstract
Abstract Background: Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies. Methods: We developed a VAT prediction score by regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case–control studies of postmenopausal breast (950 case–control pairs) and colorectal (831 case–control pairs) cancer in an independent sample in MEC. Abdominal MRI–derived VAT; circulating biomarkers of metabolic, hormonal, and inflammation dysfunctions; and ORs for incident cancer adjusted for BMI and other risk factors were assessed. Results: The final score, composed of nine biomarkers, BMI, and height, explained 11% and 15% more of the variance in VAT than BMI alone in men and women, respectively. The area under the receiver operator curve for VAT >150 cm2 was 0.90 in men and 0.86 in women. The VAT score was associated with risk of breast cancer [OR (95% confidence interval [CI]) by increasing tertiles: 1.00, 1.09 (0.86–1.39), 1.48 (1.16–1.89); Ptrend = 0.002] but not with colorectal cancer (P = 0.84), although an association [1.00, 0.98 (0.68–1.39), 1.24 (0.88–1.76); Ptrend = 0.08] was suggested for this cancer after excluding cases that occurred within 7 years of blood draw (Pheterogeneity = 0.06). Conclusions: The VAT score predicted risks of postmenopausal breast cancer and can be used for risk assessment in diverse populations. Impact: These findings provide specific evidence for a role of VAT in breast cancer.