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患有常见 IGF1R 变异的妊娠高血压疾病的女性的癌症和心血管风险。

Cancer and Cardiovascular Risk in Women With Hypertensive Disorders of Pregnancy Carrying a Common IGF1R Variant.

机构信息

Buck Institute for Research on Aging, Novato.

Graduate Group in Biostatistics, University of California, Berkeley, School of Public Health, Berkeley.

出版信息

Mayo Clin Proc. 2020 Dec;95(12):2684-2696. doi: 10.1016/j.mayocp.2020.03.037. Epub 2020 Nov 6.

Abstract

OBJECTIVE

To evaluate the impact of insulin-like growth factor 1 receptor variant rs2016347 on the risk for breast and nonbreast cancers and cardiovascular disease in women with a history of hypertensive disorders of pregnancy (HDP).

PATIENTS AND METHODS

This retrospective cohort study included all parous women in the UK Biobank with prior rs2016347 genotyping (N=204,155), with enrollment taking place from March 2006 to July 2010. History of HDP was self-reported, and outcomes included breast and all nonbreast cancers, hospital diagnoses of hypertension and cardiovascular disease, and direct blood pressure measurements.

RESULTS

Women with previous HDP had a higher risk for future hypertension and cardiovascular diagnoses, increased blood pressures, and lower risk for breast cancer compared with women without HDP, consistent with prior studies. Hazard ratios for all nonbreast cancers were unchanged. However, when taking genotype into account, HDP-positive women carrying at least 1 thymine (T) allele of rs2016347 had a lower risk for nonbreast cancer (hazard ratio, 0.59; 95% CI, 0.37 to 0.92; P=.02) and lower systolic blood pressure (-2.08±0.98 mm Hg; P=.03) compared with women with the guanine/guanine (GG) genotype with positive evidence of interaction (HDP:T allele) for both outcomes; P=.04 and P=.03, respectively.

CONCLUSION

Women who experience HDP and carry a T allele of rs2016347 have 41% lower risk for developing nonbreast cancer and a lower systolic blood pressure of 2.08 mm Hg when compared with those with the GG genotype, suggesting a possible role of the insulin-like growth factor 1 axis for both cardiovascular and cancer risk in women with HDP.

摘要

目的

评估胰岛素样生长因子 1 受体变体 rs2016347 对有妊娠高血压疾病(HDP)病史的女性患乳腺癌和非乳腺癌以及心血管疾病风险的影响。

患者和方法

这项回顾性队列研究纳入了英国生物银行中所有有先前 rs2016347 基因分型的经产妇女(N=204155),入组时间为 2006 年 3 月至 2010 年 7 月。HDP 的病史是自我报告的,结果包括乳腺癌和所有非乳腺癌、高血压和心血管疾病的医院诊断以及直接血压测量。

结果

与没有 HDP 的女性相比,有 HDP 病史的女性未来患高血压和心血管疾病的风险更高,血压更高,乳腺癌风险更低,这与之前的研究一致。所有非乳腺癌的风险比没有变化。然而,当考虑到基因型时,携带至少 1 个胸腺嘧啶(T)等位基因的 HDP 阳性女性患非乳腺癌的风险较低(风险比,0.59;95%置信区间,0.37 至 0.92;P=.02),收缩压也较低(-2.08±0.98mmHg;P=.03),与携带 HDP 阳性且有证据表明交互作用(HDP:T 等位基因)的 GG 基因型的女性相比;P=.04 和 P=.03。

结论

与携带 GG 基因型的女性相比,患有 HDP 并携带 rs2016347 的 T 等位基因的女性患非乳腺癌的风险降低 41%,收缩压降低 2.08mmHg,这表明胰岛素样生长因子 1 轴在 HDP 女性的心血管和癌症风险中可能发挥作用。

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