Huang Tianyi, Tworoger Shelley S, Hecht Jonathan L, Rice Megan S, Sood Anil K, Kubzansky Laura D, Poole Elizabeth M
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Cancer Epidemiol Biomarkers Prev. 2016 Dec;25(12):1587-1594. doi: 10.1158/1055-9965.EPI-16-0534. Epub 2016 Sep 1.
The β-adrenergic signaling pathway mediates the effects of chronic stress on ovarian cancer progression in mouse models. The relevance of this pathway to human ovarian cancer remains unknown.
We assessed tumor expression of β-adrenergic receptor (ADRB2) using tissue microarrays in 237 ovarian cancer cases from the Nurses' Health Studies (NHS/NHSII). Competing risks Cox regression was used to evaluate whether associations of reproductive, hormonal, and psychosocial factors with ovarian cancer risk differed by ADRB2. We also examined the association between tumor ADRB2 expression and ovarian cancer survival.
Forty-five (19%) cases were positive for ADRB2 staining. High levels of anxiety symptoms were positively associated with ADRB2-positive tumors (HR, 2.59; 95% confidence interval [CI], 1.15-5.84) but not with ADRB2-negative tumors (HR, 1.16; 95% CI, 0.81-1.66; P = 0.07). We observed similar results for depression. No associations were observed for job strain, caregiving stress, or widowhood for either positive or negative ADRB2 status. Lifetime ovulatory years were more strongly associated with ADRB2-positive tumors (HR per 5 years, 1.60; 95% CI, 1.15-2.21) compared with ADRB2-negative tumors (HR, 1.11; 95% CI, 0.96-1.27; P = 0.04). Significant heterogeneity by ADRB2 was also observed for parity (P = 0.01), oral contraceptive use (P = 0.03), and age at menopause (P = 0.04). Tumor expression of ADRB2 was not associated with ovarian cancer mortality (HR, 1.05; 95% CI, 0.69-1.59).
Several stress- and ovulation-related factors were differentially associated with ovarian tumors responsive to β-adrenergic signaling.
Replication in larger studies is warranted to confirm the role of β-adrenergic signaling in ovarian cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1587-94. ©2016 AACR.
在小鼠模型中，β-肾上腺素能信号通路介导慢性应激对卵巢癌进展的影响。该通路与人类卵巢癌的相关性尚不清楚。
我们使用组织微阵列评估了来自护士健康研究（NHS/NHSII）的237例卵巢癌病例中β-肾上腺素能受体（ADRB2）的肿瘤表达情况。采用竞争风险Cox回归来评估生殖、激素和心理社会因素与卵巢癌风险的关联是否因ADRB2而有所不同。我们还研究了肿瘤ADRB2表达与卵巢癌生存率之间的关联。
45例（19%）病例的ADRB2染色呈阳性。高水平的焦虑症状与ADRB2阳性肿瘤呈正相关（风险比[HR]，2.59；95%置信区间[CI]，1.15 - 5.84），但与ADRB2阴性肿瘤无关（HR，1.16；95% CI，0.81 - 1.66；P = 0.07）。对于抑郁，我们观察到了类似的结果。对于ADRB2阳性或阴性状态，工作压力、照顾压力或丧偶均未观察到相关性。与ADRB2阴性肿瘤（HR，1.11；95% CI，0.96 - 1.27；P = 0.04）相比，终生排卵年数与ADRB2阳性肿瘤的相关性更强（每5年HR，1.60；95% CI，1.15 - 2.21）。在产次（P = 0.01）、口服避孕药使用（P = 0.03）和绝经年龄（P = 0.04）方面，也观察到了ADRB2的显著异质性。肿瘤ADRB2表达与卵巢癌死亡率无关（HR，1.05；95% CI，0.69 - 1.59）。
一些与应激和排卵相关的因素与对β-肾上腺素能信号有反应的卵巢肿瘤存在差异关联。
有必要在更大规模的研究中进行重复验证，以确认β-肾上腺素能信号在卵巢癌病因学中的作用。癌症流行病学、生物标志物与预防；25(12)；1587 - 94。©2016美国癌症研究协会。
