Two genes HPC/ELAC-2 and AAT were studied in north Indian population. HPC/ELAC-2 was studied in prostate cancer cases and AAT was studied in COPD patients. HPC/ELAC-2 is considered as an important cancer-susceptibility gene in prostate cancer. There are two common polymorphisms of this gene, i.e., Ser217Leu and Ala541Thr. Alpha 1 antitrypsin is a highly polymorphic anti-elastase enzyme, especially active in the protection of alveoli and liver. In the present study, we observed the distribution of two deficient alleles PiZ and Pi S in COPD patients. We extracted the DNA from 157 prostate cancer cases, 200 COPD patients, 170 BPH and 370 healthy controls. The polymorphisms were studied by PCR-RFLP technique. The mutant genotype (Leu/Leu) of HPC/ELAC-2 was present in 9.6, 7.6 and 5.9% of BPH, cancer cases and healthy controls, respectively. Higher risk of Ser/Leu as well as Leu/Leu had shown when compared to healthy controls. That was about 1.5 and 1.7-fold (OR = 1.55; 95% CI = 0.96-2.51; OR = 1.70; 95% CI = 0.74-3.92), respectively. Risk was found to be increased in smokers and those consuming non-vegetarian diet. Our results suggest that the HPC/ELAC-2 polymorphisms, especially in localized cases, could help to predict prostate cancer risk and confirm its high prevalence of the leu/leu allele in north Indian population. Considering heterozygous PiZ genotype, we obtained an OR of 3.82 (P = 0.03). Multivariate analysis adjusted by age sex and drinking habit showed 4.15-fold increased risk for COPD in PiZ heterozygous individuals. No increased risk was observed in the individuals carrying PiS alleles.