title: Analysis of genetic variants in never-smokers with lung cancer facilitated by an Internet-based blood collection protocol: a preliminary report.
abstract: OBJECTIVE
  Germ line polymorphisms may confer susceptibility to lung cancer in never smokers, but studies in the United States have been limited by the low number of cases seen at single institutions. We hypothesized that we could use the Internet to bolster the accrual of appropriate patients.
  
  
  METHODS
  We established an Internet-based protocol to collect blood and information from patients throughout the United States. To illustrate the power of this approach, we used these samples, plus additional cases and age-matched controls from the Memorial Sloan-Kettering Cancer Center (New York, NY) and the Aichi Cancer Center (Nagoya, Japan), to analyze germ line DNA for genetic variants reportedly associated with lung cancer susceptibility. The genotypes for the polymorphisms rs763317 (intron 1) and T790M (exon 20) in the EGFR gene were determined by direct sequencing, and CHRNA3 nicotinic acetylcholine receptor single nucleotide polymorphisms (rs8034191 and rs1051730) were genotyped as part of a pilot genome-wide association study.
  
  
  RESULTS
  We successfully analyzed germ line DNA from 369 cases, including 45 obtained via the Internet, and 342 controls. A germ line EGFR T790M variant was identified in 2 of the 369 cases (0.54%; 95% confidence interval, 0.21-1.29%), and in none of the 292 controls (P = 0.21). No difference was observed in EGFR rs763317 frequency between cases and controls. Similarly, neither CHRNA3 rs8034191 nor rs1051730 were associated with lung cancer risk.
  
  
  CONCLUSIONS
  The Internet provides a way to recruit patients throughout the country for minimal risk studies. This approach could be used to facilitate studies of germ line polymorphisms in specific groups of patients with cancer.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Rekha
authors.initials: R
authors.lastname: Reddy
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.forename: Megan
authors.initials: M
authors.lastname: Harlan
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Khedoudja
authors.initials: K
authors.lastname: Nafa
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Gregory
authors.initials: G
authors.lastname: Riely
authors.forename: Vincent
authors.initials: V
authors.lastname: Miller
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Klein
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: William
authors.initials: W
authors.lastname: Pao
mesh_terms: D000368:Aged; D000465:Algorithms; D001800:Blood Specimen Collection / Q000379:methods*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D018773:Genes, erbB-1; D005843:Geography; D006801:Humans; D020407:Internet; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012907:Smoking; D014481:United States