Abstract

BackgroundOlder paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea.MethodsHistologically confirmed breast cancer cases (n = 1,011) and controls (n = 1,011) with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration.ResultsThe risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025). The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged <30 years. This association was profound in breast cancer cases in premenopausal women (OR = 1.9, 95% CI = 1.12–3.26, for paternal aged ≥40 vs. <30) (p for trend = 0.031). Although the risk of breast cancer increased as maternal age increased up to the intermediate, and then reduced; the risks in women whose mother were aged 25–29, 30–34, and ≥35 yrs at birth compared to women whose mothers were aged <25 years, were 1.2, 1.4, and 0.8, respectively, the trend was not significant (p for trend = 0.998).ConclusionThese findings suggest that older paternal age increases the risk of breast cancer in their female offspring.

Highlights

  • Older paternal age may increase the germ cell mutation rate in the offspring

  • The mean of paternal age at birth was significantly different between cases and controls (33.1 yrs vs. 32.5 yrs; Odds ratio (OR) = 1.1, 95% confidence interval (95% confidence intervals (CIs)) = 1.00–1.28 per 10 yrs), the mean of maternal age was not (28.7 yrs vs. 28.3 yrs; OR = 1.1, 95% CI = 0.97–1.28 per 10 yrs) (Table 2)

  • The association of paternal age with the risk of breast cancer was pronounced after controlling for maternal age; women whose fathers were aged 30–34, 35–39, and ≥40 yrs at their births, had 1.0, 1.0, and 1.6-fold increased risk of breast cancer compared with women whose fathers were aged

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Summary

Introduction

Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea. There have been growing evidences that prenatal factors may play an important role in determining breast cancer risk in adult life. These factors are hypothesized to affect breast cancer risk by altering the hormonal environment of the developing fetus [1], or by affecting the cumulative frequency of germ cell mutations [2,3]. Innes et al [7] suggested that there was a positive trend in risk of breast cancer with increasing paternal age in young women

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