Obesity is a risk factor for > 13
cancer sites, although it is unknown whether there is a common mechanism across sites. Evidence suggests a role for impaired
branched-chain amino acid (BCAAs;
isoleucine,
leucine,
valine) metabolism in
obesity,
insulin resistance, and immunity; thus, we hypothesized circulating BCAAs may be associated with incident
obesity-related
cancers. We analyzed participants in the prospective Women's Health Study without a history of
cancer at baseline blood collection (N = 26,711, mean age = 54.6 years [SD = 7.1]). BCAAs were quantified via NMR spectroscopy, log-transformed, and standardized. We used Cox proportional regression models adjusted for age, race, smoking, diet, alcohol, physical activity, menopausal
hormone use, Body Mass Index (BMI), diabetes, and other risk factors. The endpoint was a composite of
obesity-related
cancers, defined per the International Agency for Research on
Cancer 2016 report, over a median 24 years follow-up. Baseline BMI ≥ 30 kg/m2 compared with BMI 18.5-25.0 kg/m2 was associated with 23% greater risk of
obesity-related
cancers (n = 2751 events; multivariable HR 1.23, 95% CI 1.11-1.37). However, BCAAs were not associated with
obesity-related
cancers (multivariable HR per SD = 1.01 [0.97-1.05]). Results for individual BCAA metabolites suggested a modest association for
leucine with
obesity-related
cancers (1.04 [1.00-1.08]), and no association for
isoleucine or
valine (0.99 [0.95-1.03] and 1.00 [0.96-1.04], respectively). Exploratory analyses of BCAAs with individual sites included positive associations between
leucine and postmenopausal
breast cancer, and
isoleucine with
pancreatic cancer. Total circulating BCAAs were unrelated to
obesity-related
cancer incidence although an association was observed for
leucine with incident
obesity-related
cancer.