Scholarlink

Background <p>Physical activity is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene–physical activity interaction analysis.</p> Methods <p>Using logistic regression (1-d.f), two-step screening and testing method (EDGE), and joint tests (3-d.f), we analyzed interactions between common genetic variants across the genome and physical activity in relation to CRC risk. Self-reported physical activity levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (&lt; 8.75 MET-h/wk; 39,992 participants) and as study- and sex-specific quartiles of activity (42,602 participants).</p> Results <p>Physical activity was inversely associated with CRC risk overall (OR [active vs. inactive] = 0.85; 95% CI = 0.81–0.90). The two-step EDGE method identified an interaction between rs4779584, an intergenic variant near the <i>GREM1</i> and <i>SCG5</i> genes, and physical activity for CRC risk (<i>p</i>-interaction = 2.6 × 10<sup>−8</sup>). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75–0.85), but no significant physical activity–CRC associations among CT or TT carriers. When physical activity was modeled as quartiles, the 1-d.f. test identified that rs56906466, an intergenic variant near the <i>KCNG1</i> gene, modified the association between physical activity and CRC (<i>p</i>-interaction = 3.5 × 10<sup>−8</sup>). Stratification at this locus showed that an increase in physical activity (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72–0.82).</p> Conclusions <p>In summary, we identified two genetic variants that modified the association between physical activity and CRC risk. One of them, related to <i>GREM1</i> and <i>SCG5</i>, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be involved in the protective association between physical activity and colorectal carcinogenesis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genetic risk factors modulate the association between physical activity and colorectal cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月5日

查看全文
  • Anita R. Peoples,
  • Mireia Obón-Santacana,
  • Andre E. Kim,
  • Eric S. Kawaguchi,
  • Yubo Fu,
  • Conghui Qu,
  • Ferran Moratalla-Navarro,
  • John Morrison,
  • Yi Lin,
  • Volker Arndt,
  • Sonja I. Berndt,
  • Stephanie A. Bien,
  • D. Timothy Bishop,
  • Emmanouil Bouras,
  • Hermann Brenner,
  • Daniel D. Buchanan,
  • Peter T. Campbell,
  • Andrew T. Chan,
  • Jenny Chang-Claude,
  • David V. Conti,
  • Douglas AC. Corley,
  • Matthew A. Devall,
  • Niki Dimou,
  • David A. Drew,
  • Stephen B. Gruber,
  • Marc J. Gunter,
  • Sophia Harlid,
  • Tabitha A. Harrison,
  • Michael Hoffmeister,
  • Li Hsu,
  • Jeroen R. Huyghe,
  • Temitope O. Keku,
  • Anshul Kundaje,
  • Juan Pablo Lewinger,
  • Li Li,
  • Brigid M. Lynch,
  • Loic Le Marchand,
  • Vicente Martín,
  • Neil Murphy,
  • Christina C. Newton,
  • Shuji Ogino,
  • Sheetal Hardikar,
  • Jennifer Ose,
  • Rish K. Pai,
  • Julie R. Palmer,
  • Nikos Papadimitriou,
  • Bens Pardamean,
  • Andrew J. Pellatt,
  • Mila Pinchev,
  • Elizabeth A. Platz,
  • John D. Potter,
  • Gad Rennert,
  • Edward A. Ruiz-Narvaez,
  • Lori C. Sakoda,
  • Robert E. Schoen,
  • Anna Shcherbina,
  • Mariana C. Stern,
  • Yu-Ru Su,
  • Claire E. Thomas,
  • Yu Tian,
  • Konstantinos K. Tsilidis,
  • Caroline Y. Um,
  • Franzel J. B. van Duijnhoven,
  • Bethany Van Guelpen,
  • Kala Visvanathan,
  • Jun Wang,
  • Emily White,
  • Alicja Wolk,
  • Michael O. Woods,
  • Anna H. Wu,
  • Cornelia M. Ulrich,
  • Ulrike Peters,
  • W. James Gauderman,
  • Victor Moreno

摘要

Background

Physical activity is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene–physical activity interaction analysis.

Methods

Using logistic regression (1-d.f), two-step screening and testing method (EDGE), and joint tests (3-d.f), we analyzed interactions between common genetic variants across the genome and physical activity in relation to CRC risk. Self-reported physical activity levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk; 39,992 participants) and as study- and sex-specific quartiles of activity (42,602 participants).

Results

Physical activity was inversely associated with CRC risk overall (OR [active vs. inactive] = 0.85; 95% CI = 0.81–0.90). The two-step EDGE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and physical activity for CRC risk (p-interaction = 2.6 × 10−8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75–0.85), but no significant physical activity–CRC associations among CT or TT carriers. When physical activity was modeled as quartiles, the 1-d.f. test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between physical activity and CRC (p-interaction = 3.5 × 10−8). Stratification at this locus showed that an increase in physical activity (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72–0.82).

Conclusions

In summary, we identified two genetic variants that modified the association between physical activity and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be involved in the protective association between physical activity and colorectal carcinogenesis.