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Association between the ACE-I/D polymorphism and nicotine dependence amongst patients with lung cancer
Sergej Nadalin1, Veljko Flego2, Sanja Dević Pavlić1
1Department of Medical Biology and Genetics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
Abstract:
The biologically active peptide angiotensin II is cleaved from angiotensinogen by the renin and the angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system (RAS). RAS may be important in the etiology of nicotine dependence by influencing dopaminergic signaling. In the present study, the association between an insertion/deletion (I/D) polymorphism of ACE and nicotine dependence amongst patients with lung cancer was assessed. To date, several studies have shown the relevance of this polymorphic variant in both nicotine dependence and lung cancer. However, the present study is the first to address the potential role of the ACE-I/D polymorphism in nicotine dependence among patients with lung cancer. Genotyping was performed in 305 patients with lung cancer (males/females, 214/91). Significantly more male smokers had the ACE-I allele compared with male non-smokers (44.9 vs. 20.0%; P<0.05). The risk of smoking was ~5-fold higher for males with the ACE-I allele (ACE-II homozygous and ACE-ID heterozygous) vs. ACE-DD homozygous (odds ratio, 5.47; 95% confidence interval, 1.4-21.9; P=0.016). The pack-year smoking history in a subgroup of females with squamous cell carcinoma carrying the ACE-I allele was significantly lower compared with ACE-DD (37.1±14.1 vs. 57.0±29.1; F=4.5; P=0.046). The ACE-I/D polymorphism accounted for 17.6% of the smoking severity in this patient group (β, -0.42; multiple R2 change, 0.176; P=0.046). These results suggest that the ACE-I/D polymorphism contributes to the risk of nicotine dependence and smoking severity in lung cancer patients in a sex-specific manner.
Insights
The angiotensin-converting enzyme (ACE) I/D polymorphism influences nicotine dependence risk and smoking severity in lung cancer patients. This genetic factor shows sex-specific effects, impacting smoking behavior differently in males and females.
Area of Science:
- Genetics
- Pharmacology
- Oncology
Background:
- The renin-angiotensin system (RAS), involving angiotensin-converting enzyme (ACE), plays a role in dopaminergic signaling relevant to nicotine dependence.
- Previous studies suggest a link between the ACE insertion/deletion (I/D) polymorphism and both nicotine dependence and lung cancer.
- This research uniquely investigates the ACE-I/D polymorphism's role in nicotine dependence specifically within a lung cancer patient cohort.
Purpose of the Study:
- To assess the association between the ACE I/D polymorphism and nicotine dependence in patients with lung cancer.
- To determine if the ACE I/D polymorphism influences smoking severity in this patient group.
- To explore potential sex-specific effects of the ACE I/D polymorphism on smoking behavior.
Main Methods:
- Genotyping was performed on 305 lung cancer patients (214 males, 91 females).
- Statistical analyses, including odds ratios and regression models, were used to evaluate the association between ACE genotype and smoking status/severity.
- Comparisons were made between different ACE genotypes (I/D, II, ID, DD) and smoking behaviors.
Main Results:
- Male smokers were significantly more likely to possess the ACE-I allele compared to male non-smokers (44.9% vs. 20.0%, P<0.05).
- Males with the ACE-I allele had a ~5-fold higher risk of smoking compared to ACE-DD homozygotes (OR, 5.47; P=0.016).
- In female lung cancer patients with squamous cell carcinoma, carrying the ACE-I allele was associated with lower pack-year smoking history compared to ACE-DD (37.1 vs. 57.0, P=0.046).
- The ACE-I/D polymorphism explained 17.6% of the variation in smoking severity in this cohort (P=0.046).
Conclusions:
- The ACE-I/D polymorphism is associated with nicotine dependence risk and smoking severity in lung cancer patients.
- These effects appear to be sex-specific, with different implications for males and females.
- The findings highlight the genetic contribution of the ACE I/D polymorphism to smoking behaviors in the context of lung cancer.
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