title: Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer.
abstract: Lung cancer is the most common fatal cancer among Danish men, and the incidence rate is increasing among women. In a case-cohort study, we have investigated the occurrence of lung cancer in relation to a high-risk haplotype, previously identified for breast cancer among post-menopausal women, and in relation to the closely linked polymorphisms XPD Asp312Asn and Lys751Gln. Among 54220 members of a Danish prospective cohort study aged 50-64 at entry, 265 lung cancer cases were identified and a sub-cohort comprising 272 individuals was used for comparison. Among women in the 50-55 year age interval, homozygous carriers of the high-risk haplotype were at increased risk of lung cancer (RR=7.02, 95% CI=1.88-26.18). In the 56-60 year and 61-70 year age intervals, no associations were observed. Among men, no statistically significant associations were found in any age interval. Female homozygous carriers of the variant allele of XPD Lys751Gln were at significantly increased risk of lung cancer in the two younger age-intervals (50-55 years: RR=5.60, 95% CI=1.18-26.45, 56-60 years: RR=10.60, 95% CI=1.50-75.64). Among men, carriers of the variant allele of XPD Lys751Gln had a non-significantly increased risk of lung cancer in the youngest age interval (RR=6.38, 95% CI=0.74-54.90). When the polymorphisms in XPD Asp312Asn and Lys751Gln were mutually adjusted, XPD Asp312Asn was not associated with increased risk of cancer. We found no interaction between genotypes and duration of smoking. In conclusion, two regions of chromosome 19q13.2-3 seem to be associated with risk of lung cancer.
authors.affiliation: National Institute of Occupational Health, DK-2100 Copenhagen O, Denmark. ubv@ami.dk
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Imke
authors.initials: I
authors.lastname: Laros
authors.forename: Nicklas R
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Birthe L
authors.initials: BL
authors.lastname: Thomsen
authors.forename: Helle
authors.initials: H
authors.lastname: Bak
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Bukowy
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
authors.forename: Ole
authors.initials: O
authors.lastname: Raaschou-Nielsen
mesh_terms: D000368:Aged; D001483:Base Sequence; D002353:Carrier State; D002888:Chromosomes, Human, Pair 19; D004265:DNA Helicases; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human