NFKB1/NFKBIa polymorphisms are associated with the progression of cervical carcinoma in HPV-infected postmenopausal women from rural area.

Abstract

Human papillomavirus (HPV) is considered as the major etiological agent for development of cervical cancer but alone is not sufficient enough. So, other environmental factors and host genetic background may play an important role in the development of cervical cancer. HPV carries a minimal amount of structural and regulatory proteins so it is apparently dependent on its host for survival. NF-κB/IkB system plays an important regulatory role in the apoptotic pathway. In the present study, a total of 575 consecutive subjects including 285 cases (45 cervical pre-cancerous and 240 invasive cervical carcinoma) and 290 age- and ethnicity-matched controls recruited from Lok Nayak Jai Prakash Hospital and Safdarjung Hospital, New Delhi between July 2009 to July 2013 were genotyped for NFKB1 -94 insertion/deletion (rs28362491) and NFKBIa 3'-UTR2758A > G (rs696) polymorphism by PCR-RFLP followed by sequencing. We observed a positive association of NFKB1 -94 insertion/insertion (II) and NFKBIa 3'-UTR 2758 GG genotypes with the progression of cervical carcinoma. Cervical cancer patients were found more pronounce to be a carrier of II + GG genotype of both the SNPs. We also noticed that HPV-infected postmenopausal women having higher parity along with the history of tobacco consumption and who carries insertion allele of NFKB1 -94 polymorphism in association of GG genotype of NFKBIa 3'-UTR polymorphism, were more susceptible to develop cervical carcinoma. II + GG genotype together were found to have direct proportionality with the aggressiveness of cervical carcinoma. In conclusion, alteration in the gene map of NFKB1/NFKBIa helps in the progression of cervical cancer accompanied by HPV infection in postmenopausal women from rural residential setup who had higher parity along with history of tobacco consumption.