title: FAM13A locus in COPD is independently associated with lung cancer - evidence of a molecular genetic link between COPD and lung cancer.
abstract: Recent genome-wide association studies have reported a FAM13A variant on chromosome 4q22.1 is associated with lung function and COPD. We examined this variant in a case-control study of current or former smokers with chronic obstructive pulmonary disease (COPD, n = 458), lung cancer (n = 454), or normal lung function (n = 488). Sex, age, and smoking history were comparable between groups. We confirmed the FAM13A variant (rs7671167) confers a protective effect on smoking-related COPD alone (C allele odds ratio [OR] = 0.79, P = 0.013, and CC genotype OR = 0.71, P = 0.024) and those with COPD, both with and without lung cancer (C allele OR = 0.80, P = 0.008, and CC genotype OR = 0.70, P = 0.007). The FAM13A variant also confers a protective effect on lung cancer overall (C allele OR = 0.75, P = 0.002, and CC genotype OR = 0.64, P = 0.003) even after excluding those with co-existing COPD (C allele OR = 0.67, P = 0.0007, and CC genotype OR = 0.58, P = 0.006). This was independent of age, sex, height, lung function, and smoking history. This protective effect was confined to those with nonsmall cell lung cancer (C allele OR = 0.72, P = 0.0009, and CC genotype OR = 0.61, P = 0.003). This study suggests that genetic predisposition to COPD is shared with lung cancer through shared pathogenetic factors such as the 4q22.1 locus implicating the Rho-kinase pathway.
authors.affiliation: Department of Medicine, Auckland Hospital, Auckland, New Zealand.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Young
authors.forename: Raewyn J
authors.initials: RJ
authors.lastname: Hopkins
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Hay
authors.forename: Chris F
authors.initials: CF
authors.lastname: Whittington
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Epton
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gamble
keywords: FAM13A; GTPase; association study; chronic obstructive pulmonary disease; lung cancer; polymorphism