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Variation in TP63 is associated with lung adenocarcinoma in the UK population.

ABSTRACT: Variation at TP63 has recently been shown to be associated with lung adenocarcinoma in the Asian population.To investigate how this finding translates to the European population we compared the genotypes of SNPs annotating the TP63 locus at 3q28 in 4,462 lung cancer patients, including 911 with adenocarcinoma, and 8,235 controls from the United Kingdom.A statistically significant association between adenocarcinoma risk and SNP genotype was shown: rs10937405, OR = 1.21, P = 1.82 × 10(-4); rs17429138, OR = 1.23, P = 7.49 × 10(-5); and rs4396880, OR = 1.21, P = 2.03 × 10(-4). Haplotype analysis was consistent with a single TP63 risk locus defined by SNPs rs10937405, rs17429138, and rs4396880. While no association between SNPs and small cell lung cancer was shown, the rs10937405 and rs439680 associations were significant for squamous cancer (respective P-values, 0.0022 and 0.02).These findings show TP63 variation is a risk factor for the development of lung adenocarcinoma in the UK population. Furthermore, they provide additional insight into the subtype-specificity of the 3q28 lung cancer association.Our data confirm the association of 3q28 with lung adenocarcinoma and that this association is not confined to the Asian population. Elucidating the functional basis of this association will be contingent on future fine mapping of the TP63 loci.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5108419 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Variation in TP63 is associated with lung adenocarcinoma in the UK population.

Wang Yufei Y Broderick Peter P Matakidou Athena A Vijayakrishnan Jayaram J Eisen Timothy T Houlston Richard S RS

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20110524 7

<h4>Background</h4>Variation at TP63 has recently been shown to be associated with lung adenocarcinoma in the Asian population.<h4>Methods</h4>To investigate how this finding translates to the European population we compared the genotypes of SNPs annotating the TP63 locus at 3q28 in 4,462 lung cancer patients, including 911 with adenocarcinoma, and 8,235 controls from the United Kingdom.<h4>Results</h4>A statistically significant association between adenocarcinoma risk and SNP genotype was shown ...[more]

PMID: 21610222

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Project description:BackgroundRecent trends in the incidence of lung cancer have been reported despite the decreasing rate of smoking. Lung cancer is ranked among the top causes of cancer-related deaths. The ratio of adenocarcinoma to squamous cell carcinoma, as well as the ratio of women to men, is still increasing. Human papillomavirus (HPV) has been discovered in lung cancer tissues and blood specimens, particularly in Eastern countries. However, the association between HPV infection and lung adenocarcinoma remains unclear.MethodsThis population-based cohort study was conducted using data from Taiwan's single-payer national health insurance and cancer registry databases. Data on HPV infection, cancer, sex, age, comorbidities, urbanization, and occupation were collected. The cumulative incidence rates were generated using Kaplan-Meier curves and log-rank tests. COX regression analysis was used to estimate the hazard ratios of factors associated with cancer occurrence. We used data from 2007 and 2015. The cases were matched with sex and age in a 1:2 manner with 939,874 HPV+ and 1,879,748 HPV- individuals, respectively.ResultsThe adjusted hazard ratios [95% confidence interval (CI)] for HPV infection in all lung cancers were 1.539 (1.436-1.649), male lung cancer 1.434 (1.312-1.566), female lung cancer 1.742 (1.557-1.948), squamous cell carcinoma (SCC) 1.092 (0.903-1.320), male SCC 1.092 (0.903-1.320), female SCC 0.949 (0.773-1.164), adenocarcinoma 1.714 (1.572-1.870), male adenocarcinoma 1.646 (1.458-1.858), and female adenocarcinoma 1.646 (1.458-1.858). The highest adjusted hazard ratio for lung cancer was chronic obstructive pulmonary disease (COPD) 1.799 (1.613-2.007), followed by male sex 1.567 (1.451-6.863) and HPV infection. The highest adjusted hazard ratio for adenocarcinoma was HPV infection 1.714 (1.572-1.870), followed by COPD 1.300 (1.102-1.533), and for SCC, male sex 5.645 (4.43-3.37), followed by COPD 2.528 (2.002-3.192).ConclusionOur study showed that HPV infection was associated with the occurrence of adenocarcinoma of the lung in both men and women but was not associated with SCC of the lung.

Dataset Information

Variation in TP63 is associated with lung adenocarcinoma in the UK population.

Publications

Variation in TP63 is associated with lung adenocarcinoma in the UK population.

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