Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts

Barbara J. Fuhrman; Steven C. Moore; Celia Byrne; Issam Makhoul; Cari M. Kitahara; Amy Berrington De González; Martha S. Linet; Elisabete Weiderpass; Hans-olov Adami; Neal D. Freedman; Linda M. Liao; Charles E. Matthews; Rachael Z. Stolzenberg-solomon; Mia M. Gaudet; Alpa V. Patel; I-min Lee; Julie E. Buring; Alicja Wolk; Susanna C. Larsson; Anna E. Prizment; Kim Robien; Michael Spriggs; David P. Check; Neil Murphy; Marc J. Gunter; Harold L. Van Dusen; Regina G. Ziegler; Robert N. Hoover

doi:10.1158/0008-5472.can-19-3093

Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts

Barbara J. Fuhrman
, Steven C. Moore
, Celia Byrne
, Issam Makhoul
, Cari M. Kitahara
, Amy Berrington De González
, Martha S. Linet
, Elisabete Weiderpass
, Hans-olov Adami
, Neal D. Freedman
, Linda M. Liao
, Charles E. Matthews
, Rachael Z. Stolzenberg-solomon
, Mia M. Gaudet
, Alpa V. Patel
, I-min Lee
, Julie E. Buring
, Alicja Wolk
, Susanna C. Larsson
, Anna E. Prizment

Kim Robien, Michael Spriggs, David P. Check, Neil Murphy, Marc J. Gunter, Harold L. Van Dusen, Regina G. Ziegler, Robert N. Hoover

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis.

Original language	English (US)
Pages (from-to)	2246-2255
Number of pages	10
Journal	Cancer Research
Volume	81
Issue number	8
DOIs	https://doi.org/10.1158/0008-5472.can-19-3093
State	Published - Apr 15 2021

Bibliographical note

Funding Information:
This work, the NIH-AARP Diet and Health study, the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study, the U.S. Radiologic Technologists (USRT) cohort study, and longitudinal follow-up of the Prostate, Lung, Colon and Ovarian Cancer Trial (PLCO) cohort were each supported by the Intramural Research Program of the NCI, NIH, Department of Health and Human Services (DHHS; Z99 CA999999): S. Moore, C. Kitahara, A. Berrington de Gonz?lez, M. Linet, N. Freedman, L. Liao, C. Matthews, R. Stolzenberg- Solomon, R. Ziegler, R. Hoover. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort: M. Gaudet, A. Patel. The Iowa Women's Health Study was supported by a grant from the NCI (R01 CA39742): K. Robien, A. Prizment. The Swedish Mammography Cohort was supported by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare and the Swedish Cancer Foundation: A. Wolk. The WHS was supported by grants from the NCI and the National Heart, Lung, and Blood Institute (CA047988, CA182913, HL043851, HL080467, and HL099355): J. Buring, I. Lee. The Women's Lifestyle and Health project was supported by the Swedish Cancer Society and the Swedish Research Council: A. Wolk. The funding organizations had no role in the study design, or in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.

Funding Information:
This work, the NIH-AARP Diet and Health study, the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study, the U.S. Radiologic Technologists (USRT) cohort study, and longitudinal follow-up of the Prostate, Lung, Colon and Ovarian Cancer Trial (PLCO) cohort were each supported by the Intramural Research Program of the NCI, NIH, Department of Health and Human Services (DHHS; Z99 CA999999): S. Moore, C. Kitahara, A. Berrington de González, M. Linet, N. Freedman, L. Liao, C. Matthews, R. Stolzenberg-Solomon, R. Ziegler, R. Hoover. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort: M. Gaudet, A. Patel. The Iowa Women’s Health Study was supported by a grant from the NCI (R01 CA39742): K. Robien, A. Prizment. The Swedish Mammography Cohort was supported by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare and the Swedish Cancer Foundation: A. Wolk. The WHS was supported by grants from the NCI and the National Heart, Lung, and Blood Institute (CA047988, CA182913, HL043851, HL080467, and HL099355): J. Buring, I. Lee. The Women’s Lifestyle and Health project was supported by the Swedish Cancer Society and the Swedish Research Council: A. Wolk. The funding organizations had no role in the study design, or in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.

Publisher Copyright:
© 2021 American Association for Cancer Research.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Body Mass Index
Breast Neoplasms/epidemiology
Child
Cohort Studies
Colonic Neoplasms/epidemiology
Endometrial Neoplasms/epidemiology
Europe/epidemiology
Female
Humans
Liver Neoplasms/epidemiology
Lung Neoplasms/epidemiology
Melanoma/epidemiology
Menarche/physiology
Middle Aged
Neoplasms/epidemiology
Proportional Hazards Models
Risk
United States/epidemiology
Urinary Bladder Neoplasms/epidemiology

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Meta-Analysis
Research Support, N.I.H., Intramural

Publisher link

10.1158/0008-5472.can-19-3093

http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-19-3093

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Cite this

Fuhrman, B. J., Moore, S. C., Byrne, C., Makhoul, I., Kitahara, C. M., Berrington De González, A., Linet, M. S., Weiderpass, E., Adami, H., Freedman, N. D., Liao, L. M., Matthews, C. E., Stolzenberg-solomon, R. Z., Gaudet, M. M., Patel, A. V., Lee, I., Buring, J. E., Wolk, A., Larsson, S. C., ... Hoover, R. N. (2021). Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts. Cancer Research, 81(8), 2246-2255. https://doi.org/10.1158/0008-5472.can-19-3093

Fuhrman, BJ, Moore, SC, Byrne, C, Makhoul, I, Kitahara, CM, Berrington De González, A, Linet, MS, Weiderpass, E, Adami, H, Freedman, ND, Liao, LM, Matthews, CE, Stolzenberg-solomon, RZ, Gaudet, MM, Patel, AV, Lee, I, Buring, JE, Wolk, A, Larsson, SC, Prizment, AE, Robien, K, Spriggs, M, Check, DP, Murphy, N, Gunter, MJ, Van Dusen, HL, Ziegler, RG & Hoover, RN 2021, 'Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts', Cancer Research, vol. 81, no. 8, pp. 2246-2255. https://doi.org/10.1158/0008-5472.can-19-3093

@article{e69a8984cb1247b3b54d9a02f5ac3b1c,

title = "Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts",

abstract = "The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95\% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95\% CI, 0.89-0.94), liver cancer (HR = 0.92; 95\% CI, 0.85-0.99), melanoma (HR = 0.95; 95\% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95\% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95\% CI, 0.96-0.99), lung (HR = 0.98; 95\% CI, 0.96-0.99), and breast (HR = 0.98; 95\% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis.",

keywords = "Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Body Mass Index, Breast Neoplasms/epidemiology, Child, Cohort Studies, Colonic Neoplasms/epidemiology, Endometrial Neoplasms/epidemiology, Europe/epidemiology, Female, Humans, Liver Neoplasms/epidemiology, Lung Neoplasms/epidemiology, Melanoma/epidemiology, Menarche/physiology, Middle Aged, Neoplasms/epidemiology, Proportional Hazards Models, Risk, United States/epidemiology, Urinary Bladder Neoplasms/epidemiology",

author = "Fuhrman, \{Barbara J.\} and Moore, \{Steven C.\} and Celia Byrne and Issam Makhoul and Kitahara, \{Cari M.\} and \{Berrington De Gonz{\'a}lez\}, Amy and Linet, \{Martha S.\} and Elisabete Weiderpass and Hans-olov Adami and Freedman, \{Neal D.\} and Liao, \{Linda M.\} and Matthews, \{Charles E.\} and Stolzenberg-solomon, \{Rachael Z.\} and Gaudet, \{Mia M.\} and Patel, \{Alpa V.\} and I-min Lee and Buring, \{Julie E.\} and Alicja Wolk and Larsson, \{Susanna C.\} and Prizment, \{Anna E.\} and Kim Robien and Michael Spriggs and Check, \{David P.\} and Neil Murphy and Gunter, \{Marc J.\} and \{Van Dusen\}, \{Harold L.\} and Ziegler, \{Regina G.\} and Hoover, \{Robert N.\}",

note = "Funding Information: This work, the NIH-AARP Diet and Health study, the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study, the U.S. Radiologic Technologists (USRT) cohort study, and longitudinal follow-up of the Prostate, Lung, Colon and Ovarian Cancer Trial (PLCO) cohort were each supported by the Intramural Research Program of the NCI, NIH, Department of Health and Human Services (DHHS; Z99 CA999999): S. Moore, C. Kitahara, A. Berrington de Gonz?lez, M. Linet, N. Freedman, L. Liao, C. Matthews, R. Stolzenberg- Solomon, R. Ziegler, R. Hoover. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort: M. Gaudet, A. Patel. The Iowa Women's Health Study was supported by a grant from the NCI (R01 CA39742): K. Robien, A. Prizment. The Swedish Mammography Cohort was supported by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare and the Swedish Cancer Foundation: A. Wolk. The WHS was supported by grants from the NCI and the National Heart, Lung, and Blood Institute (CA047988, CA182913, HL043851, HL080467, and HL099355): J. Buring, I. Lee. The Women's Lifestyle and Health project was supported by the Swedish Cancer Society and the Swedish Research Council: A. Wolk. The funding organizations had no role in the study design, or in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. Funding Information: This work, the NIH-AARP Diet and Health study, the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study, the U.S. Radiologic Technologists (USRT) cohort study, and longitudinal follow-up of the Prostate, Lung, Colon and Ovarian Cancer Trial (PLCO) cohort were each supported by the Intramural Research Program of the NCI, NIH, Department of Health and Human Services (DHHS; Z99 CA999999): S. Moore, C. Kitahara, A. Berrington de Gonz{\'a}lez, M. Linet, N. Freedman, L. Liao, C. Matthews, R. Stolzenberg-Solomon, R. Ziegler, R. Hoover. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort: M. Gaudet, A. Patel. The Iowa Women{\textquoteright}s Health Study was supported by a grant from the NCI (R01 CA39742): K. Robien, A. Prizment. The Swedish Mammography Cohort was supported by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare and the Swedish Cancer Foundation: A. Wolk. The WHS was supported by grants from the NCI and the National Heart, Lung, and Blood Institute (CA047988, CA182913, HL043851, HL080467, and HL099355): J. Buring, I. Lee. The Women{\textquoteright}s Lifestyle and Health project was supported by the Swedish Cancer Society and the Swedish Research Council: A. Wolk. The funding organizations had no role in the study design, or in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",

year = "2021",

month = apr,

day = "15",

doi = "10.1158/0008-5472.can-19-3093",

language = "English (US)",

volume = "81",

pages = "2246--2255",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "8",

}

TY - JOUR

T1 - Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts

AU - Fuhrman, Barbara J.

AU - Moore, Steven C.

AU - Byrne, Celia

AU - Makhoul, Issam

AU - Kitahara, Cari M.

AU - Berrington De González, Amy

AU - Linet, Martha S.

AU - Weiderpass, Elisabete

AU - Adami, Hans-olov

AU - Freedman, Neal D.

AU - Liao, Linda M.

AU - Matthews, Charles E.

AU - Stolzenberg-solomon, Rachael Z.

AU - Gaudet, Mia M.

AU - Patel, Alpa V.

AU - Lee, I-min

AU - Buring, Julie E.

AU - Wolk, Alicja

AU - Larsson, Susanna C.

AU - Prizment, Anna E.

AU - Robien, Kim

AU - Spriggs, Michael

AU - Check, David P.

AU - Murphy, Neil

AU - Gunter, Marc J.

AU - Van Dusen, Harold L.

AU - Ziegler, Regina G.

AU - Hoover, Robert N.

N1 - Funding Information: This work, the NIH-AARP Diet and Health study, the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study, the U.S. Radiologic Technologists (USRT) cohort study, and longitudinal follow-up of the Prostate, Lung, Colon and Ovarian Cancer Trial (PLCO) cohort were each supported by the Intramural Research Program of the NCI, NIH, Department of Health and Human Services (DHHS; Z99 CA999999): S. Moore, C. Kitahara, A. Berrington de Gonz?lez, M. Linet, N. Freedman, L. Liao, C. Matthews, R. Stolzenberg- Solomon, R. Ziegler, R. Hoover. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort: M. Gaudet, A. Patel. The Iowa Women's Health Study was supported by a grant from the NCI (R01 CA39742): K. Robien, A. Prizment. The Swedish Mammography Cohort was supported by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare and the Swedish Cancer Foundation: A. Wolk. The WHS was supported by grants from the NCI and the National Heart, Lung, and Blood Institute (CA047988, CA182913, HL043851, HL080467, and HL099355): J. Buring, I. Lee. The Women's Lifestyle and Health project was supported by the Swedish Cancer Society and the Swedish Research Council: A. Wolk. The funding organizations had no role in the study design, or in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. Funding Information: This work, the NIH-AARP Diet and Health study, the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study, the U.S. Radiologic Technologists (USRT) cohort study, and longitudinal follow-up of the Prostate, Lung, Colon and Ovarian Cancer Trial (PLCO) cohort were each supported by the Intramural Research Program of the NCI, NIH, Department of Health and Human Services (DHHS; Z99 CA999999): S. Moore, C. Kitahara, A. Berrington de González, M. Linet, N. Freedman, L. Liao, C. Matthews, R. Stolzenberg-Solomon, R. Ziegler, R. Hoover. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort: M. Gaudet, A. Patel. The Iowa Women’s Health Study was supported by a grant from the NCI (R01 CA39742): K. Robien, A. Prizment. The Swedish Mammography Cohort was supported by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare and the Swedish Cancer Foundation: A. Wolk. The WHS was supported by grants from the NCI and the National Heart, Lung, and Blood Institute (CA047988, CA182913, HL043851, HL080467, and HL099355): J. Buring, I. Lee. The Women’s Lifestyle and Health project was supported by the Swedish Cancer Society and the Swedish Research Council: A. Wolk. The funding organizations had no role in the study design, or in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. Publisher Copyright: © 2021 American Association for Cancer Research.

PY - 2021/4/15

Y1 - 2021/4/15

N2 - The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis.

AB - The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis.

KW - Adolescent

KW - Adult

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Body Mass Index

KW - Breast Neoplasms/epidemiology

KW - Child

KW - Cohort Studies

KW - Colonic Neoplasms/epidemiology

KW - Endometrial Neoplasms/epidemiology

KW - Europe/epidemiology

KW - Female

KW - Humans

KW - Liver Neoplasms/epidemiology

KW - Lung Neoplasms/epidemiology

KW - Melanoma/epidemiology

KW - Menarche/physiology

KW - Middle Aged

KW - Neoplasms/epidemiology

KW - Proportional Hazards Models

KW - Risk

KW - United States/epidemiology

KW - Urinary Bladder Neoplasms/epidemiology

U2 - 10.1158/0008-5472.can-19-3093

DO - 10.1158/0008-5472.can-19-3093

M3 - Article

C2 - 33820799

SN - 0008-5472

VL - 81

SP - 2246

EP - 2255

JO - Cancer Research

JF - Cancer Research

IS - 8

ER -

Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts

Abstract

Bibliographical note

UN SDGs

Keywords

PubMed: MeSH publication types

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