Polymorphism in MnSOD Gene and Breast Cancer Risk in Kashmiri Patients: a Case Control Study

Reactive oxygen species (ROS) have been implicated in the etiology of many human diseases. Antioxidant enzymes such as MnSOD protects cells from oxidative stress and generation of ROS. A case control study, with aim to evaluate the relationship between MnSOD Ala-9Val polymorphism and breast cancer was carried out. The study included 522 subjects, including 255 cases and 267 controls, 12 samples were missing or yielded no results. Genotyping of samples were carried out using PCR-RFLP method. We observed that neither of two conditions heterozygous (MnSOD Val/Ala) or Variant/(MnSOD Ala/Ala) was significantly associated with overall breast cancer risk. The frequencies of Val and Ala allele was almost similar in cases, however, a significant association was seen in case of older women (above 45 years of age) (OR =1.98, CI=1.07-3.66, P=0.04). Also ORs were elevated in case of women using oral contraceptives carrying Val/Ala genotype. (OR=2.20; CI=0.54-8.96). In conclusion MnSOD Ala-9Val polymorphism may modify the risk for breast cancer development particularly in presence of age above 45years, oral contraceptives, and urban life style

Polymorphism of DNA repair gene XRCC1 in lung cancer among Kashmiri population

DNA repair plays a critical role in protecting the genome of the cell from insults of cancer-causing agents, such as those found in tobacco smoke. Reduced DNA repair capacity, therefore, can increase the susceptibility to smoking-related cancers. Recently, three coding polymorphisms in X-ray cross-complementing group 1 (XRCC1) DNA repair gene have been identified, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility. In humans, 70 genes are involved in the five major DNA repair pathways: direct repair, BER, NER, mismatch repair, and double-strand break repair. XRCC1 acts as a facilitator or coordinator in BER, through its interaction with poly(ADP-ribose) polymerase, DNA polymerase, and DNA ligase III. We explored the association between polymorphisms of the DNA repair gene XRCC1 codon 194 and lung cancer risk in males. The role of DNA repair gene XRCC1 in susceptibility to lung cancer has not been widely studied in Kashmir. In our case control study, the study population consisted of 70 lung cancer patients and 72 healthy controls. Cases and controls were matched by age and gender. We observed a significantly high risk of lung cancer among patients who were carriers of the variant genotype Trp/Trp (homozygous mutant) with OR = 3.33, 95% CI = 1.4 - 7.9, P = 0.0056, as compared with homozygous wild type genotype Arg/Arg and was statistically significant. We observed a high risk of about three-fold in case of the homozygous variants of codon194 Trp/Trp genotype. Cases with a codon194 Trp allele were also at high risk of developing lung cancer (OR= 2.28, 95% CI = 1.36 – 3.82, P = 0.0015) and was also statistically significant. In our study, we found that cases who smoke i.e. smokers, have higher frequency of Trp/Trp homozygous variant (36.66% vs. 14.89%) as compared with controls. We also observed a high risk of about two-fold in case of homozygous variants Trp/Trp in smokers (OR= 2.87, 95% CI = 1.06 – 7.74, P = 0.03) and observation was statistically significant. . It is thus concluded that there is an elevated risk for lung cancer in individuals with the codon194 XRCC1 polymorphism. Our study suggests that cases especially smokers with homozygous variant genotype Trp/Trp tend to be more fragile and susceptible to lung cancer as compared to non-smokers. Hence the analysis of the polymorphism of XRCC1 codon Arg194Trp may help in identifying individuals at risk of developing lung cancer