Cust Anne E, Stocks Tanja, Lukanova Annekatrin, Lundin Eva, Hallmans Göran, Kaaks Rudolf, Jonsson Håkan, Stattin Pär
Centre for MEGA Epidemiology, The University of Melbourne, Melbourne, Australia.
Breast Cancer Res Treat. 2009 Feb;113(3):567-76. doi: 10.1007/s10549-008-9958-8. Epub 2008 Mar 11.
It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk, however the epidemiological evidence remains inconclusive. We conducted a case-control study nested in a prospective cohort in Northern Sweden, to clarify the associations of body mass index (BMI), leptin, adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk. We also investigated whether these associations may be modified by age at diagnosis, tumour stage, and oestrogen and progesterone receptor status. During follow-up, 561 women developed invasive breast cancer and 561 matched controls were selected. Conditional logistic regression was used to calculate odds ratios (OR) as estimates of relative risk, and 95% confidence intervals (CI). The associations of BMI, leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II-IV (P (heterogeneity) all <0.05). These factors were significantly inversely associated with risk in the group of stage I tumours, with ORs for top vs. bottom tertile for BMI of 0.48 (95% CI, 0.30-0.78, P (trend) = 0.004); leptin, 0.64 (95% CI, 0.41-1.00, P (trend) = 0.06); and HbA1c, 0.47 (95% CI, 0.28-0.80, P (trend) = 0.005). For stage II-IV tumours, there was a suggestion of an increased risk with higher levels of these factors. There were no significant differences in the associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status. This prospective study suggests that BMI, leptin and HbA1c influence breast tumour initiation and progression.
据推测，胰岛素抵抗及相关代谢因素可能会影响乳腺癌风险，然而流行病学证据仍不确凿。我们在瑞典北部的一个前瞻性队列中开展了一项病例对照研究，以阐明体重指数（BMI）、瘦素、脂联素、C肽和糖化血红蛋白（HbA1c）与乳腺癌风险之间的关联。我们还研究了这些关联是否会因诊断时的年龄、肿瘤分期以及雌激素和孕激素受体状态而有所改变。在随访期间，561名女性患浸润性乳腺癌，选取了561名匹配的对照。采用条件逻辑回归计算比值比（OR）作为相对风险的估计值，并计算95%置信区间（CI）。根据肿瘤诊断为I期还是II-IV期，BMI、瘦素和HbA1c与乳腺癌风险的关联存在显著差异（所有P（异质性）均<0.05）。在I期肿瘤组中，这些因素与风险显著负相关，BMI最高三分位数与最低三分位数的OR为0.48（95%CI，0.30-0.78，P（趋势）=0.004）；瘦素为0.64（95%CI，0.41-1.00，P（趋势）=0.06）；HbA1c为0.47（95%CI，0.28-0.80，P（趋势）=0.005）。对于II-IV期肿瘤，这些因素水平较高时有风险增加的迹象。在诊断时年龄或肿瘤受体状态的亚组中，BMI、瘦素、脂联素、C肽和HbA1c与乳腺癌风险的关联无显著差异。这项前瞻性研究表明，BMI、瘦素和HbA1c会影响乳腺肿瘤的发生和进展。
