Canadian Neighbor Pharmacy: Results of a-Antitrypsin and Neutrophil Elastase Imbalance and Lung Cancer Risk

Control subjects were 2 years older than case patients, on average, but had a similar gender ratio and ethnic background (Table 2). Compared to case patients, control subjects were less likely to be cigarette smokers, to have a history of COPD or environmental tobacco smoke exposure, or to have a positive family history of lung cancer in their first-degree relatives.

Deficient PI1 types were significantly overrepresented among case patients compare to control subjects (p < 0.05) [Table 3]. For the two ELA2 SNP sites, the frequency distribution of alleles and genotypes at Rep_a was similar between case patients and control subjects, but differed at Rep_b. Specifically, the allele G at Rep_b was overrepresented among case patients. We then compared intragenic haplotypes between case patients and control subjects (Table 3, lower portion) using the haplotype score test. There was an overall strong association (judged by global and simulated p values) between the two SNPs and lung cancer risk, particularly with haplotypes T-G and G-A. These two SNPs showed a strong LD in the case patients (D’ approximately equal to 1.0) and a weak LD in the control group (D’ = 0.81), suggesting that they may have different functionality toward the development of lung cancer. No correlation existed between the two SNPs in case patients or control subjects (r2 = 0.01), reflecting the disparate allele frequencies of the two markers in the study population. All that you need about medicine on Canadian Neighbor Pharmacy. This information will be usful for you.

Since only a minority of our study subjects were non-US white persons, we repeated the analyses restricting them to US white persons only. The results for the entire study group and for US whites only were very similar. We provide information in Table 4 with regard to the frequencies of the PI1 allele type and the ELA2 haplotype among American Indians and other minority groups compared to the US whites in our study.

To assess the effects of A1ATD allele types and Rep_a/ Rep_b haplotypes on lung cancer risk, we built multivariable models estimating the independent and interactive effects of the two genes on lung cancer risk. All models were adjusted for age and gender, with tobacco smoke exposure, family lung cancer history, and COPD as covari-ates. Among the three alternative mendelian patterns, the dominant model best fitted the data, showing that carriers of the A1ATD allele or ELA2 haplotype T-G have a 2.0-fold or 4.1-fold increased risk, respectively (Table 5). Therefore, an individual with an a1-antitrypsin-deficient allele and a T-G haplotype had a 6.1-fold (mean [± SD], 2.0 + 4.1) increased risk of lung cancer. Under the same model, we observed the following significant interactive effect of the PI1 allele type and the ELA2 haplotype: carrying a haplotype G-G was not associated with an increased risk, but carrying both an a1-antitrypsin-defi-cient allele and a haplotype G-G carried a 2.6-fold higher risk for developing lung cancer (Table 5, lower portion).

Table 2—Selected Characteristics of 305 Case Patients and 338 Control Subjects Enrolled in 1997-2002, Mayo Clinic

Table 3—Allele Frequencies and Haplotype Analysis of PI1 and ELA2 Genes

Table 4—PI1 Allele and ELA2 Haplotype Frequencies by Ethnicity

Table 5—Age and Gender-Adjusted Effects of A1ATD Allele and ELA2 Haplotypes on Lung Cancer Risk