Albers Frances E M, Swain Christopher T V, Lou Makayla W C, Dashti S Ghazaleh, Rinaldi Sabina, Viallon Vivian, Karahalios Amalia, Brown Kristy A, Gunter Marc J, Milne Roger L, English Dallas R, Lynch Brigid M
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Cancer Epidemiol Biomarkers Prev. 2025 Apr 3;34(4):541-549. doi: 10.1158/1055-9965.EPI-24-1304.
Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Furthermore, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)-positive breast cancer.
This was a case-cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study. We measured insulin, c-peptide, IGF-1, insulin-like growth factor binding protein-3, and biomarkers of inflammatory and sex-steroid hormone pathways. Poisson regression with a robust variance estimator was used to estimate risk ratios (RR) and 95% confidence intervals (95% CI) for ER-positive breast cancer per doubling plasma concentration and for quartiles, without and with adjustment for other, potentially confounding biomarkers.
ER-positive breast cancer risk was not associated with doubling of insulin (RR = 0.97, 95% CI, 0.82-1.14) or c-peptide (RR = 1.01, 95% CI, 0.80-1.26). Risk seemed to decrease with doubling IGF-1 (RR = 0.80, 95% CI, 0.62-1.03) and insulin-like growth factor binding protein-3 (RR = 0.62, 95% CI, 0.41-0.90). RRs were not meaningfully different when exposures were modeled as quartiles. RRs were less than unity but imprecise after adjustment for inflammatory and sex-steroid hormone biomarkers.
Circulating insulin, c-peptide, and IGF-1 were not positively associated with risk of ER-positive breast cancer in this case-cohort analysis of postmenopausal women.
Associations between insulin and c-peptide and risk of ER-positive breast cancer in postmenopausal women are likely to be weak.
胰岛素样生长因子-1（IGF-1）浓度升高会增加绝经后乳腺癌风险，但胰岛素和C肽的相关证据有限。此外，并非所有研究都考虑了来自其他生物学途径的生物标志物的潜在混杂因素，也并非所有研究都局限于雌激素受体（ER）阳性乳腺癌。
这是一项对墨尔本协作队列研究中1223名绝经后女性（347例ER阳性乳腺癌患者）进行的病例队列研究。我们测量了胰岛素、C肽、IGF-1、胰岛素样生长因子结合蛋白-3以及炎症和性甾体激素途径的生物标志物。使用具有稳健方差估计器的泊松回归来估计血浆浓度每增加一倍以及四分位数时ER阳性乳腺癌的风险比（RR）和95%置信区间（95%CI），不调整和调整其他潜在混杂生物标志物。
ER阳性乳腺癌风险与胰岛素增加一倍（RR = 0.97，95%CI，0.82 - 1.14）或C肽增加一倍（RR = 1.01，95%CI，0.80 - 1.26）无关。随着IGF-1增加一倍（RR = 0.80，95%CI，0.62 - 1.03）和胰岛素样生长因子结合蛋白-3增加一倍（RR = 0.62，95%CI，0.41 - 0.90），风险似乎降低。当将暴露因素建模为四分位数时，RR没有显著差异。在调整炎症和性甾体激素生物标志物后，RR小于1但不精确。
在这项绝经后女性病例队列分析中，循环胰岛素、C肽和IGF-1与ER阳性乳腺癌风险无正相关。
绝经后女性中胰岛素和C肽与ER阳性乳腺癌风险之间的关联可能较弱。
