Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
Usher Institute and CRUK Edinburgh Centre, University of Edinburgh, Edinburgh, United Kingdom.
Int J Cancer. 2020 Sep 15;147(6):1535-1547. doi: 10.1002/ijc.32929. Epub 2020 Mar 13.
Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. We analyzed data from 1,126 cases (aged 18-74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case-control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Among controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years and 18 months, respectively. For women ≥50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20-0.83) and 0.71 (95% CI 0.51-0.98) for ≥19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumors (p-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Reproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions.
非洲裔女性的早发性和雌激素受体(ER)阴性癌症比例高于欧洲裔女性。发病年龄和 ER 状态的风险因素分布和相关性的差异可能解释了这种差异。我们分析了来自加纳基于人群的病例对照研究中 1126 例(年龄 18-74 岁)浸润性乳腺癌病例和 2106 例对照的数据。使用多分类逻辑回归模型调整潜在混杂因素后,估计了月经和生殖因素的比值比(OR)和 95%置信区间(CI)。在对照组中,初潮、产次、初产年龄和母乳喂养/妊娠的中位数分别为 15 岁、4 次、20 岁和 18 个月。对于年龄≥50 岁的女性,产次和延长母乳喂养与降低风险相关:与未生育相比,>5 次产次的 OR 为 0.40(95%CI 0.20-0.83),≥19 个月与<13 个月母乳喂养/妊娠的 OR 为 0.71(95%CI 0.51-0.98),这与 ER 无关。相比之下,对于更早发病的病例(<50 岁),产次与 ER 阴性肿瘤的风险增加相关(ER 异质性 p 值=0.02),但延长母乳喂养可以抵消这种风险。内在样亚型也观察到类似的关联。初潮和初产年龄的关系不太一致。生殖风险因素的分布与欧洲人群不同,但与其他人群一样,按诊断年龄和 ER 状态存在病因异质性。生殖模式和亚型异质性的差异与亚型分布的种族差异一致。