title: Association between genetic variations in surfactant protein d and emphysema, interstitial pneumonia, and lung cancer in a Japanese population.
abstract: Surfactant protein D (SFTPD) is a lung-specific anti-inflammatory factor that antagonizes inflammation by inhibiting oxidative stress and stimulating innate immunity. Variations in SFTPA2 and SFTPB, genes for other surfactant proteins, have been associated with lung cancer. We therefore investigated associations between SFTPD variations and lung cancer as well as emphysema and interstitial pneumonia, which are characterized by chronic inflammation from which lung cancer often arises. DNA from 1342 autopsy samples, including those from 140 subjects with lung cancer, was investigated. The single nucleotide polymorphism (SNP) rs721917, which results in methionine being exchanged for threonine at amino acid 11 (the Met11Thr variation), tended to be associated with emphysema and was associated with interstitial pneumonia and lung cancer. A haplotype analysis revealed that the haplotypes associated with emphysema and lung cancer differed from that associated with interstitial pneumonia, suggesting a differential role for SFTPD in the development of these diseases. A mediating analysis did not reveal a mediating effect exerted by emphysema or interstitial pneumonia on lung cancer. Our results suggested that SFTPD plays a role in the development of lung cancer and that the role for lung cancer may differ from that for interstitial pneumonia.
authors.affiliation: Department of Pulmonary Medicine, Infection and Oncology, the Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan. tishii@nms.ac.jp
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishii
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ikeda
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Makiko Naka
authors.initials: MN
authors.lastname: Mieno
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.forename: Kozui
authors.initials: K
authors.lastname: Kida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005819:Genetic Markers; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D007564:Japan; D016015:Logistic Models; D017563:Lung Diseases, Interstitial / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011656:Pulmonary Emphysema / Q000235:genetics*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D037663:Pulmonary Surfactant-Associated Protein D