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

Fuhrman, Barbara J., Moore, Steven C., Byrne, Celia, Makhoul, Issam, Kitahara, Cari M., Berrington de González, Amy, Linet, Martha S., Weiderpass, Elisabete, Adami, Hans-Olov, Freedman, Neal D., Liao, Linda M., Matthews, Charles E., Stolzenberg-Solomon, Rachael Z., Gaudet, Mia M., Patel, Alpa V., Lee, I-Min, Buring, Julie E., Wolk, Alicja, Larsson, Susanna C., Prizment, Anna E., Robien, Kim, Spriggs, Michael, Check, David P., Murphy, Neil, Gunter, Marc J., Van Dusen, Harold L., Ziegler, Regina G., Hoover, Robert N.·2021·Cancer Research

Published version of a preprint

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. Significance: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.

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Metadata

Authors
Fuhrman, B. J., Moore, S. C., Byrne, C., Makhoul, I., Kitahara, C. M., Berrington de González, A., Linet, M. S., Weiderpass, E., Adami, H.-O., Freedman, N. D., Liao, L. M., Matthews, C. E., Stolzenberg-Solomon, R. Z., Gaudet, M. M., Patel, A. V., Lee, I.-M., Buring, J. E., Wolk, A., Larsson, S. C., Prizment, A. E., Robien, K., Spriggs, M., Check, D. P., Murphy, N., Gunter, M. J., Van Dusen, H. L., Ziegler, R. G., & Hoover, R. N.
Venue
Cancer Research
Published
2021-04-05
Volume
81
Issue
8
Pages
2246-2255
ISSN
  • 0008-5472
  • 1538-7445
Cited by
75
References
6
Language
en
Funders
  • Department of Health and Human Services NCI Memorial Sloan Kettering Cancer Center NIH (Z99 CA999999)
  • NCI (R01 CA39742)
  • NCI National Heart, Lung, and Blood Institute (CA047988, CA182913, HL043851, HL080467, HL099355)

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