Fortner Renée T, Vitonis Allison F, Schock Helena, Hüsing Anika, Johnson Theron, Fichorova Raina N, Fashemi Titilayo, Yamamoto Hidemi S, Tjønneland Anne, Hansen Louise, Overvad Kim, Boutron-Ruault Marie-Christine, Kvaskoff Marina, Severi Gianluca, Boeing Heiner, Trichopoulou Antonia, Benetou Vassiliki, La Vecchia Carlo, Palli Domenico, Sieri Sabina, Tumino Rosario, Matullo Giuseppe, Mattiello Amalia, Onland-Moret N Charlotte, Peeters Petra H, Weiderpass Elisabete, Gram Inger Torhild, Jareid Mie, Quirós J Ramón, Duell Eric J, Sánchez Maria-Jose, Chirlaque María Dolores, Ardanaz Eva, Larrañaga Nerea, Nodin Björn, Brändstedt Jenny, Idahl Annika, Khaw Kay-Tee, Allen Naomi, Gunter Marc, Johansson Mattias, Dossus Laure, Merritt Melissa A, Riboli Elio, Cramer Daniel W, Kaaks Rudolf, Terry Kathryn L
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.
Ob/Gyn Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA.
J Ovarian Res. 2017 Mar 20;10(1):20. doi: 10.1186/s13048-017-0315-6.
Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening.
We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression.
CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (p ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination.
This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.
卵巢癌早期检测标志物CA125、CA15.3、HE4和CA72.4在健康女性中存在差异，限制了它们在筛查中的应用。
我们在欧洲癌症与营养前瞻性调查（EPIC）的一项巢式病例对照研究中，评估了对照组（n = 1910）中生活方式和生殖因素与这些标志物之间的横断面关系。在巢式病例对照研究中的绝经后女性（n = 590例）中，评估了针对标志物相关性进行调整的预测模型在判别能力上的改善情况。使用广义线性模型计算CA125、CA15.3和HE4的几何均值。使用逻辑回归评估CA72.4高于或低于检测限的情况。使用条件逻辑回归对早期检测预测进行建模。
绝经后女性的CA125浓度较低，而CA15.3浓度较高（p≤0.02）。在绝经后女性中，多产且绝经年龄较大的女性CA125较高（p≤0.02），但在报告接受卵巢切除术、子宫切除术、曾使用仅含雌激素的激素疗法或当前吸烟的女性中较低（p<0.01）。体重较重的女性和既往吸烟者的CA15.3浓度较高（p≤0.03）。HE4在采血时年龄较大的女性和当前吸烟者中较高，并且与口服避孕药使用时间、产次和绝经年龄呈负相关（≤0.02）。未观察到与CA72.4的关联。在预测模型中针对标志物的相关性进行调整并未改善判别能力。
本研究深入探讨了健康女性中卵巢癌早期检测标志物的变异来源，并为基于流行病学因素个体化设定标志物切点的效用提供了信息。
