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1.  Individual and Cumulative Effects of GWAS Susceptibility Loci in Lung Cancer: Associations after Sub-Phenotyping for COPD 
PLoS ONE  2011;6(2):e16476.
Epidemiological studies show that approximately 20–30% of chronic smokers develop chronic obstructive pulmonary disease (COPD) while 10–15% develop lung cancer. COPD pre-exists lung cancer in 50–90% of cases and has a heritability of 40–77%, much greater than for lung cancer with heritability of 15–25%. These data suggest that smokers susceptible to COPD may also be susceptible to lung cancer. This study examines the association of several overlapping chromosomal loci, recently implicated by GWA studies in COPD, lung function and lung cancer, in (n = 1400) subjects sub-phenotyped for the presence of COPD and matched for smoking exposure. Using this approach we show; the 15q25 locus confers susceptibility to lung cancer and COPD, the 4q31 and 4q22 loci both confer a reduced risk to both COPD and lung cancer, the 6p21 locus confers susceptibility to lung cancer in smokers with pre-existing COPD, the 5p15 and 1q23 loci both confer susceptibility to lung cancer in those with no pre-existing COPD. We also show the 5q33 locus, previously associated with reduced FEV1, appears to confer susceptibility to both COPD and lung cancer. The 6p21 locus previously linked to reduced FEV1 is associated with COPD only. Larger studies will be needed to distinguish whether these COPD-related effects may reflect, in part, associations specific to different lung cancer histology. We demonstrate that when the “risk genotypes” derived from the univariate analysis are incorporated into an algorithm with clinical variables, independently associated with lung cancer in multivariate analysis, modest discrimination is possible on receiver operator curve analysis (AUC = 0.70). We suggest that genetic susceptibility to lung cancer includes genes conferring susceptibility to COPD and that sub-phenotyping with spirometry is critical to identifying genes underlying the development of lung cancer.
doi:10.1371/journal.pone.0016476
PMCID: PMC3033394  PMID: 21304900
2.  FAM13A locus in COPD is independently associated with lung cancer – evidence of a molecular genetic link between COPD and lung cancer 
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.
doi:10.2147/TACG.S15758
PMCID: PMC3681173  PMID: 23776362
lung cancer; chronic obstructive pulmonary disease; FAM13A; association study; polymorphism; GTPase
3.  Study was not designed to test the hypothesis 
BMJ : British Medical Journal  2007;335(7626):899.
doi:10.1136/bmj.39381.395197.BE
PMCID: PMC2048865  PMID: 17974655
4.  Lung Cancer Susceptibility Model Based on Age, Family History and Genetic Variants 
PLoS ONE  2009;4(4):e5302.
Background
Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer.
Methodology/Principal Findings
We screened 157 candidate single nucleotide polymorphisms (SNP) in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases) and identified 30 SNPs associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers) and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk.
Conclusions/Significance
Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.
doi:10.1371/journal.pone.0005302
PMCID: PMC2668761  PMID: 19390575
5.  The effect of ambient air pollution on respiratory health of school children: a panel study 
Environmental Health  2008;7:16.
Background
Adverse respiratory effects of particulate air pollution have been identified by epidemiological studies. We aimed to examine the health effects of ambient particulate air pollution from wood burning on school-age students in Christchurch, New Zealand, and to explore the utility of urine and exhaled breath condensate biomarkers of exposure in this population.
Methods
A panel study of 93 male students (26 with asthma) living in the boarding house of a metropolitan school was undertaken in the winter of 2004. Indoor and outdoor pollution data was continuously monitored. Longitudinal assessment of lung function (FEV1 and peak flow) and symptoms were undertaken, with event studies of high pollution on biomarkers of exposure (urinary 1-hydroxypyrene) and effect (exhaled breath condensate (EBC) pH and hydrogen peroxide concentration).
Results
Peak levels of air pollution were associated with small but statistically significant effects on lung function in the asthmatic students, but not healthy students. No significant effect of pollution could be seen either on airway inflammation and oxidative stress either in healthy students or students with asthma. Minor increases in respiratory symptoms were associated with high pollution exposure. Urinary 1-hydroxypyrene levels were raised in association with pollution events by comparison with low pollution control days.
Conclusion
There is no significant effect of ambient wood-smoke particulate air pollution on lung function of healthy school-aged students, but a small effect on respiratory symptoms. Asthmatic students show small effects of peak pollution levels on lung function. Urinary 1-hydroxypyrene shows potential as a biomarker of exposure to wood smoke in this population; however measurement of EBC pH and hydrogen peroxide appears not to be useful for assessment of population health effects of air pollution.
Some of the data presented in this paper has previously been published in Kingham and co-workers Atmospheric Environment, 2006 Jan; 40: 338–347 (details of pollution exposure), and Cavanagh and co-workers Sci Total Environ. 2007 Mar 1;374(1):51-9 (urine hydroxypyrene data).
doi:10.1186/1476-069X-7-16
PMCID: PMC2427023  PMID: 18479529
6.  The New Zealand Asthma and Allergy Cohort Study (NZA2CS): Assembly, Demographics and Investigations 
BMC Public Health  2007;7:26.
Background
Asthma and allergy are highly prevalent in industrialised countries. Longitudinal and cross-sectional studies have identified a number of potential risk factors for these conditions, including genetic and environmental factors, with significant gene-environment relationships. Birth cohort studies have been proposed as an important tool to explore these risk factors, particularly exposures in early life that are associated with later disease or protection from disease. This paper describes the establishment of a birth cohort in New Zealand.
Methods
A birth cohort was established in 1996 in Christchurch and Wellington and infants recruited between 1997–2001. Expectant mothers were recruited by midwives. Children and mothers have undergone assessment by serial questionnaires, environmental assessment including mould and allergen exposure, skin-prick testing, and at age six years are undergoing full assessment for the presence of asthma, atopy and allergic disease, including genetic assessment.
Results
A total of 1105 children have been recruited, and the retention rate at fifteen months was 91.4%. 15.2% of the children at recruitment have been identified as Maori. A positive family history of asthma, eczema or hay fever has been reported in 84% of children. All children have now been assessed at fifteen months and 685 children from the cohort have reached age six years and have completed the six year assessment.
Conclusion
The cohort is fully assembled, and assessment of children is well advanced, with good retention rates. The study is well placed to address many current hypotheses about the risk factors for allergic disease and asthma.
doi:10.1186/1471-2458-7-26
PMCID: PMC1819373  PMID: 17397526

Results 1-6 (6)