Buck Institute for Research On Aging, 8001 Redwood Blvd, Novato, CA, 94945, USA.
Graduate Group in Biostatistics, School of Public Health, University of California, Berkeley, CA, USA.
Breast Cancer Res Treat. 2023 Jan;197(1):149-159. doi: 10.1007/s10549-022-06789-9. Epub 2022 Nov 4.
Preeclampsia has been inconsistently associated with altered later life risk of cancer. This study utilizes the Nurses' Health Study 2 (NHS2) to determine if the future risk of breast and non-breast cancers in women who experience preeclampsia is modified by carrying a protective variant of rs2016347, a functional insulin-like growth factor receptor-1 (IGF1R) single nucleotide polymorphism.
This retrospective cohort study completed within the NHS2 evaluated participants enrolled in 1989 and followed them through 2015, with a study population of 86,751 after exclusions. Cox proportional hazards models both with and without the impact of rs2016347 genotype were used to assess the risk of invasive breast cancer, hormone receptor-positive (HR+) breast cancer, and non-breast cancers.
Women with preeclampsia had no change in risk of all breast, HR+ breast, or non-breast cancers when not considering genotype. However, women carrying at least one T allele of rs2016347 had a lower risk of HR+ breast cancer, HR 0.67, 95% CI: 0.47-0.97, P = 0.04, with interaction term P = 0.06. For non-breast cancers as a group, women carrying a T allele had an HR 0.76, 95% CI: 0.53-1.08, P = 0.12, with interaction term P = 0.26.
This retrospective cohort study found that women with preeclampsia who carry a T allele of IGF1R rs2016347 had a reduced future risk of developing HR+ breast cancer, and a reduced but not statistically significant decreased risk of non-breast cancers suggesting a possible role for the IGF-1 axis in the development of cancer in these women.
子痫前期与晚年癌症风险增加的关系不一致。本研究利用护士健康研究 2 （NHS2）来确定经历子痫前期的女性中，携带 rs2016347 保护性变体的未来乳腺癌和非乳腺癌风险是否会发生改变，rs2016347 是一种功能性胰岛素样生长因子受体 1（IGF1R）单核苷酸多态性。
这项在 NHS2 内完成的回顾性队列研究评估了 1989 年入组并随访至 2015 年的参与者，排除后研究人群为 86751 人。使用 Cox 比例风险模型，同时考虑和不考虑 rs2016347 基因型的影响，评估浸润性乳腺癌、激素受体阳性（HR+）乳腺癌和非乳腺癌的风险。
不考虑基因型时，子痫前期妇女的所有乳腺癌、HR+乳腺癌或非乳腺癌风险均无变化。然而，至少携带一个 rs2016347 T 等位基因的女性患 HR+乳腺癌的风险较低，HR 为 0.67，95%CI：0.47-0.97，P=0.04，交互项 P=0.06。对于非乳腺癌，携带 T 等位基因的女性 HR 为 0.76，95%CI：0.53-1.08，P=0.12，交互项 P=0.26。
这项回顾性队列研究发现，患有子痫前期且携带 IGF1R rs2016347 T 等位基因的女性未来患 HR+乳腺癌的风险降低，而非乳腺癌的风险虽有所降低但无统计学意义，提示 IGF-1 轴在这些女性癌症发生中可能发挥作用。
