Environment and Breast Cancer: Science Review

Evidence From Humans
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Association of paternal age at birth and the risk of breast cancer in offspring: a case control study
Choi, J. Y., Lee, K. M., Park, S. K., Noh, D. Y., Ahn, S. H., Yoo, K. Y., Kang, D. BMC Cancer. 2005. 5, 143.
Topic area
Early life exposures
Study design
Hospital based case-control
Funding agency
Other: 2001 Good Health R&D Projects, Minister of
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Number of Controls
Controls: 1011
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Cases: consecutive series of breast cancer patients admitted to three teaching hospitals located in Seoul, Korea between 1995 and 2003. Controls: Non-cancer patients admitted to the same hospitals as the cases in the same period and of healthy women who participated in the community health screening program provided by a teaching hospital located in Seoul in 2003, frequency-matched to cases by 10-years of birth group and menopausal status. Ex: subjects with missing value of either maternal or paternal age, with previous history of cancer or previous history of hysterectomy and/or oophorectomy due to cervical, ovarian cancer or its precursors.
Comment about participation selection
Controls were selected in hospitals, a potential for selection bias
Exposure Investigated
Exposures investigated
Maternal age, paternal age
How exposure was measured
Questionnaire, in person
Exposure assessment comment
Parental age at birth reported by participants
Statistical Analysis
Breast cancer outcome investigated
Primary incident breast cancer
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Adjusted for family history of breast cancer in 1st or 2nd degree relatives, lifetime estrogen exposure duration, and age of the other parent. Other covariants including age, education, age at full-term pregnancy or nulliparous, cigarette smoking, frequen
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Description of major analysis
Unconditional logistic regression was used to calculate ORs and 95% CIs, adjusting for potential confounders. Stratified analysis by menopausal status was performed.
Strength of associations reported
Paternal age: 1.6 (1.04 - 2.32), even greater for premenopausal women OR = 1.9, 95% CI = 1.12-3.26, for paternal aged >or=40 vs. <30
Maternal age: 0.8 (0.55 - 1.27)
Results Comments
Older paternal age was associated with an increased risk of breast cancer.
BACKGROUND: Older 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. METHODS: Histologically 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. RESULTS: The 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 >or=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 >or=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 >or=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). CONCLUSION: These findings suggest that older paternal age increases the risk of breast cancer in their female offspring.
Author address
Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799 Korea. miso77@snu.ac.kr