Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk

被引：4

作者：

Tian, Yu ^{[1
,2
]}

Lin, Yi ^{[3
]}

Qu, Conghui ^{[3
]}

Arndt, Volker ^{[4
]}

Baurley, James W. ^{[5
,6
]}

Berndt, Sonja I. ^{[7
]}

Bien, Stephanie A. ^{[3
]}

Bishop, D. Timothy ^{[8
]}

Brenner, Hermann ^{[4
,9
,10
]}

Buchanan, Daniel D. ^{[11
,12
,13
]}

Budiarto, Arif ^{[5
]}

Campbell, Peter T. ^{[14
]}

Carreras-Torres, Robert ^{[15
,16
,17
,18
]}

Casey, Graham ^{[19
]}

Chan, Andrew T. ^{[20
,21
,22
,23
,24
,25
]}

Chen, Rui ^{[1
]}

Chen, Xuechen ^{[4
]}

Conti, David V. ^{[26
]}

Diez-Obrero, Virginia ^{[15
,16
,17
]}

Dimou, Niki ^{[27
]}

Drew, David A. ^{[20
,21
]}

Figueiredo, Jane C. ^{[28
,29
]}

Gallinger, Steven ^{[30
]}

Giles, Graham G. ^{[31
,32
,33
]}

Gruber, Stephen B. ^{[34
]}

Gunter, Marc J. ^{[27
,35
]}

Harlid, Sophia ^{[36
]}

Harrison, Tabitha A. ^{[3
]}

Hidaka, Akihisa ^{[3
]}

Hoffmeister, Michael ^{[4
]}

Huyghe, Jeroen R. ^{[3
]}

Jenkins, Mark A. ^{[31
]}

Jordahl, Kristina M. ^{[3
,37
]}

Joshi, Amit D. ^{[24
]}

Keku, Temitope O. ^{[38
]}

Kawaguchi, Eric ^{[26
]}

Kim, Andre E. ^{[26
]}

Kundaje, Anshul ^{[39
,40
]}

Larsson, Susanna C. ^{[41
]}

Marchand, Loic Le ^{[42
]}

Lewinger, Juan Pablo ^{[26
]}

Li, Li ^{[43
]}

Moreno, Victor ^{[15
,16
,17
,44
]}

Morrison, John ^{[26
]}

Murphy, Neil ^{[27
]}

Nan, Hongmei ^{[45
,46
]}

Nassir, Rami ^{[47
]}

Newcomb, Polly A. ^{[3
,37
]}

Obon-Santacana, Mireia ^{[15
,16
,17
]}

Ogino, Shuji ^{[23
,24
,48
,49
]}

机构：

[1] Capital Med Univ, Sch Publ Hlth, Beijing, Peoples R China

[2] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[3] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA

[4] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[5] Bina Nusantara Univ, Bioinformat & Data Sci Res Ctr, Jakarta, Indonesia

[6] BioRealm LLC, Walnut, CA USA

[7] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA

[8] Univ Leeds, Leeds Inst Canc & Pathol, Leeds, England

[9] Natl Ctr Tumor Dis NCT, German Canc Res Ctr DKFZ, Div Prevent Oncol, Heidelberg, Germany

[10] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[11] Univ Melbourne, Dept Clin Pathol, Colorectal Oncogenom Grp, Parkville, Vic 3010, Australia

[12] Univ Melbourne, Ctr Canc Res, Victorian Comprehens Canc Ctr, Parkville, Vic 3010, Australia

[13] Royal Melbourne Hosp, Genom Med & Family Canc Clin, Parkville, Vic, Australia

[14] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA

[15] Bellvitge Biomed Res Inst IDIBELL, ONCOBELL Program, Radiobiol & Canc Grp, Barcelona, Spain

[16] Catalan Inst Oncol, Oncol Data Analyt Program, Barcelona, Spain

[17] Consortium Biomed Res Epidemiol & Publ Hlth CIBERE, Madrid, Spain

[18] Girona Biomed Res Inst Dr Josep Trueta IDIBGI, Digest Dis & Microbiota Grp, Girona 17190, Spain

[19] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[20] Harvard Med Sch, Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA USA

[21] Harvard Med Sch, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA USA

[22] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA

[23] Broad Inst Harvard & MIT, Cambridge, MA USA

[24] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[25] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA

[26] Univ Southern Calif, Keck Sch Med, Dept Populat & Publ Hlth Sci, Div Biostat, Los Angeles, CA USA

[27] Int Agcy Res Canc, Nutr & Metab Branch, Lyon, France

[28] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Med, Los Angeles, CA USA

[29] Univ Southern Calif, Keck Sch Med, Dept Populat & Publ Hlth Sci, Los Angeles, CA USA

[30] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[31] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia

[32] Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia

[33] Monash Univ, Sch Clin Sci Monash Hlth, Precis Med, Clayton, Vic, Australia

[34] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA

[35] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[36] Umea Univ, Dept Radiat Sci, Oncol Unit, Umea, Sweden

[37] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA USA

[38] Univ North Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA

[39] Stanford Univ, Dept Genet, Stanford, CA USA

[40] Stanford Univ, Dept Comp Sci, Stanford, CA USA

[41] Karolinska Inst, Inst Environm Med, Stockholm, Sweden

[42] Univ Hawaii, Canc Ctr, Honolulu, HI USA

[43] Univ Virginia, Dept Family Med, Charlottesville, VA USA

[44] Univ Barcelona UB, Sch Med & Hlth Sci, Dept Clin Sci, Lhospitalet De Llobregat, Barcelona, Spain

[45] Richard M Fairbanks Sch Publ Hlth, Dept Global Hlth, Indianapolis, IN USA

[46] Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN USA

[47] Umm Al Quraa Univ, Sch Med, Dept Pathol, Mecca, Saudi Arabia

[48] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Program MPE Mol Pathol Epidemiol, Boston, MA USA

[49] Tokyo Med & Dent Univ, Inst Sci Tokyo, Tokyo, Japan

[50] Huntsman Canc Inst, Salt Lake City, UT USA

来源：

BRITISH JOURNAL OF CANCER | 2024年 / 130卷 / 10期

基金：

中国国家自然科学基金; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; ESTROGEN PLUS PROGESTIN; SUSCEPTIBILITY LOCI; POSTMENOPAUSAL WOMEN; COLON-CANCER; IDENTIFICATION; VARIANT; METAANALYSIS; SUBTYPES; SCAN;

D O I：

10.1038/s41416-024-02638-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 x 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 x 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 x 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

引用

页码：1687 / 1696

页数：10

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