Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious

Baron, John A.

doi:10.1093/oxfordjournals.bmb.a011533

Cited by 174 publications

(86 citation statements)

References 117 publications

(43 reference statements)

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“…This may be explained by the fact that cigarette smoking alters the metabolism of estrogen and tends to suppress estrogen levels (48). Although HRT use is a risk factor for endometrial cancer, this antiestrogenic effect of smoking (49,50) has been associated with an ϳ50% reduction in the risk of endometrial cancer (51)(52)(53)(54)(55). This antiestrogenic effect may be due to the decreased ovarian production of estrogens or altered estrogen metabolism (55,56).…”

Section: Discussionmentioning

confidence: 99%

Hormone Replacement Therapy and Lung Cancer Risk

Schabath¹,

Wu²,

Vassilopoulou‐Sellin

et al. 2004

Clinical Cancer Research

165

129

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Purpose: To date, there are few published data regarding the use of hormone replacement therapy (HRT) and lung cancer risk. Therefore, we analyzed data regarding HRT use from a large case-control study designed to study genetic susceptibility to lung cancer to determine whether HRT affected risk of lung cancer.Experimental Design: In a secondary analysis, we compared self-reported HRT use among 499 women with lung cancer and 519 healthy age-matched controls.Results: HRT use was associated with an overall reduced risk of 34% [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.51-0.89] of lung cancer, after adjusting for age, ethnicity, smoking status, education, body mass index, and menopausal status. The use of estrogen replacement therapy alone was associated with a 35% reduction in lung cancer risk (OR, 0.65; 95% CI, 0.47-0.89) and the use of combination therapy (estrogen and progestin) was associated with a 39% reduction in lung cancer risk (OR, 0.61; 95% CI, 0.40 -0.92). HRT use was also associated with a statistically significantly reduced risk of lung cancer in current smokers (OR, 0.59; 95% CI, 0.38 -0.92), but the risk estimates were not statistically significant in never (OR, 0.72; 95% CI, 0.37-1.40) or former smokers (OR, 0.73; 95% CI, 0.46 -1.15). In addition, as the cigarette pack-years increased among ever smokers, the protective effect diminished, so that light smokers appeared to benefit the most from HRT use. Decreased lung cancer risks were also evident when the data were stratified by age, ethnicity, and body mass index. The joint effects of HRT use and mutagen sensitivity suggest that HRT use modifies lung cancer risk for genetically susceptible women. HRT use was also associated with a lower risk of death and improved survival compared with the women not taking HRT. To provide a possible biological mechanism to explain our findings, we compared plasma levels of insulin-like growth factor I in users and nonusers, and demonstrated that HRT use was associated with statistically significantly lower insulin-like growth factor I levels for both cases and controls compared with non-HRT users.Conclusions: These data suggest an association of HRT use with a decrease in lung cancer risk. However, there are several limitations to this secondary analysis, requiring that the data be viewed with caution, and confirmation is required in well-designed hypothesis driven studies. The biological role of HRT in lung cancer remains understudied, and only extensive research can yield new insights into the mechanisms underlying a protective effect of HRT for lung cancer.

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Section: Discussionmentioning

confidence: 99%

Hormone Replacement Therapy and Lung Cancer Risk

Schabath¹,

Wu²,

Vassilopoulou‐Sellin

et al. 2004

Clinical Cancer Research

165

129

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“…Involvement of PI3 /AKT pathway in response to nicotine was also supported by our observation that the expression of p70S6, a downstream target of AKT gene [42], was downregulated in VTA ( Table 2). The observed effects of nicotine on the mRNA expression of PTEN and AKT/ p70S6 warrant further investigation, which may shed light on the associations between nicotine and cancer [32,47,2].…”

Section: Region-specific Transcriptional Response To Chronic Nicotinementioning

confidence: 94%

Region-specific transcriptional response to chronic nicotine in rat brain

et al. 2001

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Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, i.e. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978±0.0035 from 0.941 ±0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=0.7; P<10 −14 ) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K + channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration.

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“…The decreased incidence of Parkinson's disease in smokers has consistently been demonstrated in both prospective and retrospective studies, is dose-and time-dependent, and does not appear to be due to increased mortality [11,[13][14][15][16][17]. Although the component in cigarette smoke that confers this apparent neuroprotective action remains to be identified, numerous studies using both culture systems and experimental animal models suggest that nicotine may play an important role, as detailed below.…”

Section: Nicotine and Nicotinic Agonists For Neuroprotectionmentioning

confidence: 97%

“…In addition, the finding that stimulation of the nicotinic cholinergic system ameliorates cognitive declines [12] suggests that nicotinic acetylcholine receptor (nAChR) drugs may be useful in treating some of the nondopaminergic deficits associated with Parkinson's disease, such as dementia that develops in 50% of Parkinson's disease patients with disease progression [1][2][3][4]. Lastly, there is very compelling epidemiological evidence demonstrating a negative association between smoking and Parkinson's disease that has been attributed to the nicotine in tobacco, at least in part [11,[13][14][15][16][17].Altogether these observations suggest that the nicotinic cholinergic system represents a promising direction for much-needed therapies for Parkinson's disease. Moreover, the identification of unique nAChR subtypes in the nigrostriatal system (as discussed later) may allow for the development of drugs that selectively target this debilitating neurological disorder.…”

mentioning

confidence: 99%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics. Keywordsα-ConotoxinMII; Nicotine; Nicotinic; Parkinson's disease; Nigrostriatal; Striatum Parkinson's disease and the nicotinic cholinergic systemThe pathological hallmarks of Parkinson's disease are the presence of intracellular Lewy bodies and an extensive degeneration of the nigrostriatal dopaminergic system. [1][2][3][4]. There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4].Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

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Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious

Cited by 174 publications

References 117 publications

Hormone Replacement Therapy and Lung Cancer Risk

Hormone Replacement Therapy and Lung Cancer Risk

Region-specific transcriptional response to chronic nicotine in rat brain

Nicotinic receptors as CNS targets for Parkinson's disease

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