Tobacco alkaloid derivatives as inhibitors of breast cancer aromatase

Kadohama, N.; Shintani, Keiji; Osawa, Yoshio

doi:10.1016/0304-3835(93)90060-m

Cited by 36 publications

(27 citation statements)

References 33 publications

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“…Two other studies have also found reduced risk of breast cancer associated with smoking only in the period after a first birth (Band et al, 2002;Lash and Aschengrau, 2002). Some compounds in cigarettes inhibit the aromatisation of androgens to oestrogens and enhance the formation of oestrodiol metabolites with low oestrogenic activity (Michnovicz et al, 1986;Kadohama et al, 1993). Hence it has been suggested that smoking in later life may be associated with reduced risk of breast cancer through mechanisms related to decreased oestrogen activity (Band et al, 2002).…”

Section: Smoking After First Birthmentioning

confidence: 98%

Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis

2004

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It has been suggested that the period between puberty and first birth is a time when the breast is particularly susceptible to carcinogenic effects. In a cohort of 3047 women aged 60 -79 years (N ¼ 139 breast cancer cases), we found no association between smoking before the birth of a first child and breast cancer risk: fully adjusted (for age, number of children, age at birth of first child, age at menarche, age at menopausal, hysterectomy and/or oophorectomy, ever use of oral contraception, use of hormone replacement therapy, alcohol consumption, body mass index, childhood and adulthood social class) odds ratio 1.06 (95% confidence interval: 0.72, 1.56). The pooled estimate from a meta-analysis of our study and 11 previously published studies (N ¼ 6528 cases) was 1.07 (0.94, 1.22). We conclude that smoking prior to the birth of a first child is not associated with increased risk of breast cancer.

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Section: Smoking After First Birthmentioning

confidence: 98%

Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis

2004

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“…12,36 The higher breast cancer risk observed in women who started smoking before their FFTP, and therefore before full breast differentiation, is in agreement with such hypothesis. An antiestrogenic effect able to protect against breast cancer has also been hypothesized, through changes in hepatic estrogen metabolism 37,38 or by inhibiting the aromatization of androgens into estrogens, [37][38][39][40] although a large pooled analysis with data from 13 studies, including EPIC, showed that BMI-adjusted mean serum concentrations of estradiol and other sex hormones were higher in heavy smokers than in nonsmokers. 41 Such a protective effect, unless it is of outstanding magnitude, is expected to be most apparent when circulating levels of estrogens are low, that is after menopause, among MHT non users, as observed in previous studies.…”

Section: Epidemiologymentioning

confidence: 99%

Active and passive cigarette smoking and breast cancer risk: Results from the EPIC cohort

et al. 2014

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Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack‐years and a dose‐response relationship with increasing pack‐years of smoking between menarche and first full‐term pregnancy (FFTP). Studies with comprehensive quantitative life‐time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05–1.28], 1.14 [1.04–1.25] and 1.10 [1.01–1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack‐years from menarche to FFTP (1.73 [1.29–2.32] for every increase of 20 pack‐years) while pack‐years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34–0.82 for every increase of 20 pack‐years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.

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“…al., 1986; Kadohama et al, 1993). The effect of nicotine on brain aromatase availability was examined with [ 11 C]vorozole in six female baboons before and after exposure to IV nicotine at .015 and .03 mg/kg; doses shown to produce plasma levels in the range encountered in cigarette smokers (Biegon et al, 2010).…”

Section: In Vivo Visualization Of Aromatase With Positron Emissionmentioning

confidence: 99%

In vivo visualization of aromatase in animals and humans

Biegon

2016

Frontiers in Neuroendocrinology

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Aromatase catalyzes the last and obligatory step in the biosynthesis of estrogens across species. In vivo visualization of aromatase can be performed using positron emission tomography (PET) with radiolabeled aromatase inhibitors such as [11C]vorozole. PET studies in rats, monkeys and healthy human subjects demonstrate widespread but heterogeneous aromatase availability in brain and body, which appears to be regulated in a species, sex and region-specific manner. Thus, aromatase availability is high in brain amygdala and in ovaries of all species examined to date, with males demonstrating higher levels than females in all comparable organs. However, the highest concentrations of aromatase in the human brain are found in specific nuclei of the thalamus while the highest levels in rats and monkeys are found in the amygdala. Regional brain aromatase availability is increased by androgens and inhibited by nicotine. Future studies may improve diagnosis and treatment in brain disorders and cancers overexpressing aromatase.

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Tobacco alkaloid derivatives as inhibitors of breast cancer aromatase

Cited by 36 publications

References 33 publications

Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis

Smoking before the birth of a first child is not associated with increased risk of breast cancer: findings from the British Women's Heart and Health Cohort Study and a meta-analysis

Active and passive cigarette smoking and breast cancer risk: Results from the EPIC cohort

In vivo visualization of aromatase in animals and humans

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