title: Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.
abstract: Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Begumpet, Telangana State, India. Electronic address: ayyadevarapavani@gmail.com.
authors.forename: A Pavani
authors.initials: AP
authors.lastname: Sowjanya
authors.affiliation: Sir Ronald Ross Institute of Tropical and Communicable Diseases, Nallakunta, Hyderabad, Telangana State, India. Electronic address: dr.meera@gmail.com.
authors.forename: Meera
authors.initials: M
authors.lastname: Rao
authors.affiliation: Mediciti Institute of Medical Sciences (MIMS) Campus, Ghanpur Village, Medchal Mandal, Ranga Reddy District, 501401 Telangana State, India. Electronic address: haripriya2603@gmail.com.
authors.forename: Haripriya
authors.initials: H
authors.lastname: Vedantham
authors.affiliation: Mediciti Institute of Medical Sciences (MIMS) Campus, Ghanpur Village, Medchal Mandal, Ranga Reddy District, 501401 Telangana State, India. Electronic address: kalpanabasany@gmail.com.
authors.forename: Basany
authors.initials: B
authors.lastname: Kalpana
authors.affiliation: MNJ Institute of Oncology & Regional Cancer Centre, Lakdikapool, Hyderabad, 500004 Telangana State, India. Electronic address: usharani@eth.net.
authors.forename: Usha Rani
authors.initials: UR
authors.lastname: Poli
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA. Electronic address: morgan.marks@merck.com.
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Marks
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Begumpet, Telangana State, India. Electronic address: drgenesu@yahoo.co.in.
authors.forename: M
authors.initials: M
authors.lastname: Sujatha
mesh_terms: D000328:Adult; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009566:Nitrates / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D009573:Nitrites / Q000097:blood*; D027383:Papillomaviridae / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D002577:Uterine Cervical Diseases / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000821:virology
chemical_list: D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II
keywords: Cervical cancer; HPV infection; Polymorphism; iNOS