Genetic Technologies Limited, Fitzroy, Victoria, Australia.
Phenogen Sciences Inc, Charlotte, North Carolina, USA.
Eur J Cancer Prev. 2023 Jan 1;32(1):57-64. doi: 10.1097/CEJ.0000000000000771. Epub 2022 Oct 27.
Women with a family history of ovarian cancer or a pathogenic or likely pathogenic gene variant are at high risk of the disease, but very few women have these risk factors. We assessed whether a combined polygenic and clinical risk score could predict risk of ovarian cancer in population-based women who would otherwise be considered as being at average risk.
We used the UK Biobank to conduct a prospective cohort study assessing the performance of 10-year ovarian cancer risks based on a polygenic risk score, a clinical risk score and a combined risk score. We used Cox regression to assess association, Harrell's C-index to assess discrimination and Poisson regression to assess calibration.
The combined risk model performed best and problems with calibration were overcome by recalibrating the model, which then had a hazard ratio per quintile of risk of 1.338 [95% confidence interval (CI), 1.152-1.553], a Harrell's C-index of 0.663 (95% CI, 0.629-0.698) and overall calibration of 1.000 (95% CI, 0.874-1.145). In the refined model with estimates based on the entire dataset, women in the top quintile of 10-year risk were at 1.387 (95% CI, 1.086-1.688) times increased risk, while women in the top quintile of full-lifetime risk were at 1.527 (95% CI, 1.187-1.866) times increased risk compared with the population.
Identification of women who are at high risk of ovarian cancer can allow healthcare providers and patients to engage in joint decision-making discussions around the risks and benefits of screening options or risk-reducing surgery.
有卵巢癌家族史或致病性或可能致病性基因突变的女性患该病的风险很高，但很少有女性有这些风险因素。我们评估了基于多基因和临床风险评分的综合评分是否可以预测基于人群的、被认为处于平均风险的女性的卵巢癌风险。
我们使用英国生物库进行了一项前瞻性队列研究，评估了基于多基因风险评分、临床风险评分和综合风险评分的 10 年卵巢癌风险。我们使用 Cox 回归评估相关性，使用 Harrell 的 C 指数评估区分度，使用泊松回归评估校准度。
综合风险模型表现最佳，通过重新校准模型克服了校准问题，然后该模型的每五分位风险的风险比为 1.338（95%置信区间，1.152-1.553），Harrell 的 C 指数为 0.663（95%置信区间，0.629-0.698），整体校准度为 1.000（95%置信区间，0.874-1.145）。在基于整个数据集的估计的精炼模型中，10 年风险最高五分位数的女性风险增加 1.387 倍（95%置信区间，1.086-1.688），而终生风险最高五分位数的女性风险增加 1.527 倍（95%置信区间，1.187-1.866）与人群相比。
识别出患有卵巢癌风险较高的女性，可以让医疗保健提供者和患者共同讨论筛查选择或降低风险手术的风险和益处。
