Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331 to 420 days) of baseline. Baseline plasma FGF23 was not associated with prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its co-receptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.

BackgroundEpidemiologic data suggest that parity increases risk of hormone receptor-negative breast cancer and that breastfeeding attenuates this association. Prospective data, particularly on the joint effects of higher parity and breastfeeding, are limited.MethodsWe investigated parity, breastfeeding, and breast cancer risk by hormone-receptor (estrogen (ER) and progesterone receptor (PR)) and molecular subtypes (luminal A, luminal B, HER2-enriched, and basal-like) in the Nurses’ Health Study (NHS; 1976–2012) and NHSII (1989–2013). A total of 12,452 (ER+ n = 8235; ER− n = 1978) breast cancers were diagnosed among 199,514 women. We used Cox proportional hazards models, adjusted for breast cancer risk factors, to calculate hazard ratios (HR) and 95% confidence intervals (CI).ResultsParous women had lower risk of ER+ breast cancer (vs. nulliparous, HR = 0.82 [0.77–0.88]); no association was observed for ER− disease (0.98 [0.84–1.13]; Phet = 0.03). Among parous women, breastfeeding was associated with lower risk of ER− (vs. never 0.82 [0.74–0.91]), but not ER+, disease (0.99 [0.94–1.05]; Phet < 0.001). Compared to nulliparous women, higher parity was inversely associated with luminal B breast cancer regardless of breastfeeding (≥ 3 children: ever breastfed, 0.78 [0.62–0.98]; never breastfed, 0.76 [0.58–1.00]) and luminal A disease only among women who had breastfed (≥ 3 children, 0.84 [0.71–0.99]). Basal-like breast cancer risk was suggestively higher among women with higher parity who never breastfed; associations were null among those who ever breastfed.ConclusionsThis study provides evidence that breastfeeding is inversely associated with hormone receptor-negative breast cancers, representing an accessible and cost-effective risk-reduction strategy for aggressive disease subtypes.Electronic supplementary materialThe online version of this article (10.1186/s13058-019-1119-y) contains supplementary material, which is available to authorized users.

The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996 and 1999, and breast cancer risk in a nested case-control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n = 794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI ≥ 25), several odd-chain saturated (SFA, e.g. 17:0, OR (95% CI) =1.85 (1.18-2.88), p =0.006 p <0.001), trans (TFA, e.g. 18:1, OR (95% CI) =2.33 (1.45-3.77), p <0.001, p =0.007) and dairy-derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n-7t; OR (95% CI) =1.83(1.16-2.89), p =0.005, p <0.001) were positively associated, and n-3 polyunsaturated fatty acids (n-3 PUFA, e.g. alpha-linolenic acid; OR (95% CI) =0.57 (0.36-0.89), p =0.017, p =0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI < 25 (OR (95% CI) =0.68 (0.46-0.98), p =0.05, p =0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy-derived fatty acids and inverse associations of n-3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted.