title: Effect of FHIT loss and p53 mutation on HPV-infected lung carcinoma development.
abstract: High-risk human papillomavirus (HPV)16/18 infection in the development of lung cancer has previously been identified, and fragile histidine triad (FHIT) loss and p53 mutation are frequently observed in the disease. However, the association between these factors has not been well studied. The present study aimed to further investigate the significance of HPV infection, FHIT loss and p53 mutations in the development of lung cancer and their possible associations. DNA was extracted from paraffin-embedded specimens from 88 cases of squamous cell carcinoma (SCC), 56 of adenocarcinoma (AC), 36 of small cell lung carcinoma (SCLC) and 110 non-cancer control cases of lung neoplasms. The prevalence of HPV infection was determined by polymerase chain reaction analysis, and FHIT loss and p53 mutations were detected by immunohistochemistry. The χ2, Fisher's exact and Pearson correlation tests were applied for statistical analysis. The results of the present study demonstrated that HPVL1 (the major capsid protein of HPV), HPV16 and HPV18 infection were more prevalent in the lung cancer samples compared with the non-cancer controls (all P<0.001). FHIT loss occurred more frequently in the lung cancer samples (44.44%) compared with the non-cancer controls (7.25%) (P<0.001). FHIT loss in the HPVL1-positive group was significantly increased compared with the HPVL1-negative group in the lung cancer cases and the non-cancer controls (P<0.05). In the lung cancer cases, the p53 mutation rates in the HPVL1- and HPV16/18-positive groups were significantly increased compared with the HPVL1- and HPV16/18-negative groups (P<0.05). In the 180 lung cancer cases, the coexistence rate of FHIT loss and a history of smoking was 38.33% (69/180; Pearson contingency coefficient of r=0.318; P<0.001). FHIT loss and p53 mutation exhibited a synergistic effect on HPV-associated lung cancer (Pearson contingency coefficient r=0.357, P<0.001). The present study demonstrated that FHIT loss may be important in the occurrence of lung cancer, particularly in lung SCCs. FHIT loss may therefore be used as an early indicator for lung cancer, particularly for patients with a history of smoking. HPV infection in lung tumorigenesis may, at least in part, be mediated through FHIT loss. FHIT loss and p53 mutation may coordinate together in the development of HPV-associated lung cancer, and accelerate the occurrence and development of lung cancer.
authors.affiliation: Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Yang
keywords: FHIT loss; human papillomavirus; lung cancer; p53 mutation