title: Identification and association study with lung cancer for novel insertion polymorphisms of human endogenous retrovirus.
abstract: Sequences of human endogenous retroviruses (HERVs) are members of the long terminal repeat (LTR) retrotransposon family. Although the expression of HERV has long been a topic of investigation, HERV-insertion polymorphisms are not well known, and a genetic association between HERV-insertion polymorphisms and cancer has never been reported. To identify novel HERV loci in the genome from cancer tissues, we carried out the inverse PCR method targeting a conserved LTR region of HML-2, which is the most recently acquired HERV group. Novel two insertions, HML-2_sLTR(1p13.2) and HML-2_sLTR(19q12), were identified as insertionally polymorphic solo LTRs. Furthermore, a significant prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in female never-smoking patients aged 60 years and over who had lung adenocarcinoma [versus the other genotyping; odds ratio (OR): 1.97; 95% confidence interval (CI): 1.01-3.81]. In another cohort consisting of female never-smoking patients with lung adenocarcinoma, a prevalence of HML-2_sLTR(1p13.2) homozygosity tended to be high in patients aged 60 years and over (versus the other genotyping; OR: 2.03; 95% CI: 0.96-4.29), whereas a low prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in patients <60 years old (versus the other genotyping; OR: 0.31; 95% CI: 0.11-0.94). Our results suggest that HML-2_sLTR(1p13.2) is involved with the susceptibility to lung adenocarcinoma in female never-smokers in an age-dependent manner and that other HERV polymorphisms related to human diseases might remain to be identified in the human genome.
authors.affiliation: Department of Tumor Pathology and.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kahyo
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Funai
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kurabe
authors.forename: Masaya
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tanahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Niwa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Tanioka
authors.forename: Guang
authors.initials: G
authors.lastname: Yin
authors.forename: Makiko
authors.initials: M
authors.lastname: Morita
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D017931:DNA Primers; D004198:Disease Susceptibility; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; C485839:ERVK-6 protein, human endogenous retrovirus; D014759:Viral Envelope Proteins