高い心肺体力が遺伝的要因による乳がん発症リスク上昇を抑える可能性

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2026-10-14 早稲田大学

早稲田大学と中国の西安交通大学などの研究チームは、心肺体力と遺伝的要因の組み合わせが、閉経後女性の乳がん発症リスクとどのように関連するかを調べた。英国の大規模バイオバンク「UK Biobank」に登録された閉経後女性15,199人を対象に、推定最大酸素摂取量を指標とする心肺体力と、多数の遺伝子多型の影響を統合した多遺伝子リスクスコア(PRS)を分析した。平均10.7年間の追跡期間中に547人が乳がんを発症した。解析の結果、心肺体力が最も高い群では、最も低い群に比べて乳がん発症リスクが約28%低かった。また、遺伝的リスクが高い女性の中でも、心肺体力が高い群では、低~中程度の群に比べてリスク上昇が小さかった。この傾向は特に60歳以上の女性で明確だった。本研究は、遺伝的リスクと体力を組み合わせて疾患リスクを評価する重要性を示している。ただし観察研究であり、運動によって遺伝的リスクを打ち消せることや、心肺体力を高めれば乳がんを予防できることを直接証明したものではない。

高い心肺体力が遺伝的要因による乳がん発症リスク上昇を抑える可能性

<関連情報>

閉経後女性における心肺機能、多遺伝子リスク、および乳がん:前向きコホート研究 Cardiorespiratory Fitness, Polygenic Risk, and Breast Cancer in Postmenopausal Women: A Prospective Cohort Study

Kumpei Tanisawa,Daiki Watanabe,Qian Li,Xiayue Fan,Xiaomin Sun
Medicine & Science in Sports & Exercise  Published:October 06, 2026
DOI: 10.1249/MSS.0000000000004164

Abstract

Purpose:
Although cardiorespiratory fitness (CRF) is inversely associated with breast cancer risk, whether CRF modifies the association between breast cancer polygenic risk score (PRS) and incident breast cancer remains unclear. We examined the independent and joint associations of CRF and breast cancer PRS with incident breast cancer in postmenopausal women from the UK Biobank and evaluated multiplicative and additive interactions between CRF and breast cancer PRS.

Methods:
This prospective cohort study included postmenopausal women from the UK Biobank. CRF was estimated using a submaximal cycle ergometer test, and genetic susceptibility was assessed using a breast cancer PRS. Cox proportional hazards models adjusted for established breast cancer risk factors were used to estimate hazard ratios. Multiplicative and additive interactions between CRF and PRS were evaluated, with additive interaction assessed using the relative excess risk due to interaction (RERI).

Results:
Among 15,199 postmenopausal women, 547 women developed incident breast cancer during a median follow-up of 10.7 years. Higher CRF was associated with lower risk of incident breast cancer in a dose–response manner, whereas higher PRS was associated with higher risk. Although multiplicative interaction was not significant, additive interaction analyses indicated that higher CRF was associated with attenuation of excess breast cancer risk conferred by high PRS (RERI −0.79, 95% CI −1.47 to −0.10). This attenuation was particularly evident among women aged ≥60 years.

Conclusions:
Higher CRF was associated with lower breast cancer risk and attenuation of excess breast cancer risk conferred by elevated polygenic risk, particularly among older women. These findings support the potential role of CRF in risk-stratified breast cancer prevention strategies.

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