Female reproductive factors and risk of lymphoid neoplasm: The Japan Public Health Center-based Prospective Study

Cancer Sci. 2019 Apr;110(4):1442-1452. doi: 10.1111/cas.13962. Epub 2019 Mar 9.


Although a possible role of reproductive factors in lymphomagenesis has been hypothesized, results of epidemiological studies have been inconsistent. Here, we investigated the association between reproductive factors and the risk of lymphoid neoplasm and its subgroups. We used data from a large-scale, population-based prospective study in a Japanese cohort with 42 691 eligible women aged 40-69 years from 1990 to 1994. During a mean follow up of 18.7 years, we identified 176 cases of lymphoid neoplasm and 90 of non-Hodgkin lymphoma (NHL). A multivariable-adjusted Cox proportional hazards regression model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of lymphoid neoplasms and its subgroups according to self-reported reproductive factors. Parous women had an increased risk of lymphoid neoplasm compared with nulliparous women (HR = 2.51, 95% CI, 1.03-6.13). An increased risk of lymphoid neoplasms was found in women with later onset of menarche (≤13 years old; reference: 14-15; HR = 1.75, 95% CI = 1.10-2.79: ≥16; HR = 1.93, 95% CI = 1.17-3.19: P-trend: 0.01) and a shorter menstrual cycle (28-29 days; reference: ≤27; HR = 1.60, 95% CI = 1.05-2.43, P-trend = 0.81). No association was observed between lymphoid neoplasms and other reproductive factors, including age at first birth, breastfeeding, type of menopause, or exogenous hormone use. Our study suggests that ever parity, late age at menarche and a short menstrual cycle length may be associated with the development of lymphoid neoplasms. The inconsistency seen in epidemiological research to date warrants further investigation.

Keywords: Japan; epidemiology; lymphoid neoplasms; prospective cohort; reproductive factors.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Disease Susceptibility*
  • Female
  • Follow-Up Studies
  • Humans
  • Japan / epidemiology
  • Leukemia, Lymphoid / epidemiology*
  • Leukemia, Lymphoid / etiology*
  • Lymphoma / epidemiology*
  • Lymphoma / etiology*
  • Middle Aged
  • Prospective Studies
  • Public Health Surveillance
  • Reproductive History*
  • Risk Assessment
  • Risk Factors