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. PrizmentKim 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 journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)2246-2255
Number of pages10
JournalCancer Research
Volume81
Issue number8
DOIs
StatePublished - 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.

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

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