Context: Puberty is a time of intense growth and differentiation of breast tissue and a window of susceptibility (WOS) for breast cancer. Although oxidative stress markers have been associated with breast cancer risk, it is unclear whether oxidative stress levels are different during the pubertal WOS, and if so, whether these differences are related to breast cancer susceptibility.

Methods: We measured urinary biomarkers of whole body oxidative stress (urinary F2-Isoprostanes and 8-oxodeoxyguanosine (8-oxodG)) in 158 girls (ages 6-13 years), 71 with and 87 without a breast cancer family history (BCFH) from a cohort of adolescent girls from the New York site of the LEGACY cohort (Lessons in Epidemiology and Genetics in Adults Cancer from Youth). We compared levels of urinary oxidative stress biomarkers (F2-Isoprostanes and 8-oxodG) across the pubertal window, defined by Tanner Stage (TS) of breast development, both cross-sectionally and longitudinally within girls over an 18-month follow up period.

Results: Urinary oxidative stress biomarkers were unrelated to pubertal stages in cross-sectional analyses after considering adjustments for body mass index (BMI) and BCFH. In our longitudinal analysis, we found that urinary 8-oxodG levels, but not F2-Isoprostane levels, increased with age in BCFH + girls (β = 6.12, 95%CI =0.08-12.16) compared to BCFH- girls. Higher BMI was associated with higher level of F2-Isoprostane in both cross-sectional (β = 0.02, 95%CI =0.0004-0.05) and longitudinal analysis (β = 0.02, 95%CI =0.0002-0.05).

Conclusion: These findings support that higher body mass index increases oxidative stress biomarkers over the pubertal window and that there are changes in 8-oxodG oxidative stress biomarkers in girls with a breast cancer family history compared to girls without a breast cancer family history.

背景：青春期是乳腺组织迅速生长和分化的时期，也是乳腺癌易感性（WOS）的窗口。尽管氧化应激标志物已与乳腺癌风险相关，但尚不清楚氧化应激水平在青春期WOS期间是否不同，如果存在，这些差异是否与乳腺癌易感性有关。

方法：我们测量了158名女孩（6-13岁），71名有乳腺癌家族史（BCFH）和87名女孩的全身氧化应激（尿液中的F2-异前列腺素和8-氧代脱氧鸟苷（8-oxodG））的尿液生物标志物。来自LEGACY队列纽约站点的青少年队列（青少年成人癌症的流行病学和遗传学课程）。我们比较了在18个月的随访期内，女孩横切和纵切的整个青春期窗口中的尿液氧化应激生物标志物（F2-异前列腺素和8-oxodG）的水平，由乳房发育的Tanner阶段（TS）定义。

结果：在考虑了对体重指数（BMI）和BCFH的调整后，尿液中的氧化应激生物标记物与青春期的横截面分析无关。在我们的纵向分析中，我们发现，与BCFH-女孩相比，BCFH +女孩（β= 6.12，95％CI = 0.08-12.16）随年龄的增长而增加了尿中的8-oxodG水平，而不是F2-异前列腺素水平。在横截面（β= 0.02，95％CI = 0.0004-0.05）和纵向分析（β= 0.02，95％CI = 0.0002-0.05）中，较高的BMI与F2-异前列腺素水平较高相关。

结论：这些发现支持较高的体重指数增加了青春期窗上的氧化应激生物标志物，并且与没有乳腺癌家族史的女孩相比，有乳腺癌家族史的女孩的8-oxodG氧化应激生物标志物发生了变化。