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Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.

ABSTRACT: Genome-wide association studies have associated common variations at chromosomes 5p15 and 15q25 with lung cancer risk. The 5p15 locus has also been associated with increased bladder cancer risk in a recent report. The 15q25 locus has been associated with nicotine dependence and self-reported number of cigarettes smoked per day in some studies and it was proposed that its association with lung cancer may be mediated through differences in smoking behavior. Here, we investigated the roles of variations at 5p15 (rs401681, rs402710, rs2736098 and rs2736100) and 15q25 (rs1051730 and rs8034191) in bladder cancer etiology in two case-control studies conducted separately in Los Angeles County, CA, USA (498 cases and 588 controls) and in Shanghai, China (506 cases and 530 controls). We replicated the association between the 5p15 locus and bladder cancer among non-Hispanic whites (NHW) in Los Angeles [for rs2736100, per C allele odds ratio (OR) = 1.23; 95% confidence interval (CI), 1.02-1.48; P = 0.029] and among Chinese in Shanghai (OR = 1.22; 95% CI, 1.02-1.47; P = 0.033). Both rs1051730 and rs8034191 at 15q25 were rare among Chinese. Among NHW, a significant association was found between rs8034191 and bladder cancer which persisted after adjustment for cigarette smoking status, number of cigarettes smoked per day and number of years of smoking (per C allele OR = 1.26; 95% CI, 1.04-1.54; P = 0.017). Our results support 5p15 and 15q25 as susceptibility regions for bladder cancer risk.

SUBMITTER: Gago-Dominguez M

PROVIDER: S-EPMC3026841 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.

Gago-Dominguez Manuela M Jiang Xuejuan X Conti David V DV Castelao Jose Esteban JE Stern Mariana C MC Cortessis Victoria K VK Pike Malcolm C MC Xiang Yong-Bing YB Gao Yu-Tang YT Yuan Jian-Min JM Van Den Berg David J DJ

Carcinogenesis 20101115 2

Genome-wide association studies have associated common variations at chromosomes 5p15 and 15q25 with lung cancer risk. The 5p15 locus has also been associated with increased bladder cancer risk in a recent report. The 15q25 locus has been associated with nicotine dependence and self-reported number of cigarettes smoked per day in some studies and it was proposed that its association with lung cancer may be mediated through differences in smoking behavior. Here, we investigated the roles of varia ...[more]

PMID: 21081471

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Project description:BackgroundGenome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies.MethodsGenotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided.ResultsAssociations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, P(trend) = 2 x 10(-26)), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, P(trend) = 1 x 10(-10)) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, P(trend) = 5 x 10(-8)) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, P(trend) = 2 x 10(-5); rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, P(trend) = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer.ConclusionsIn this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

Project description:With the near-future launch of geostationary pollution monitoring satellite instruments over North America, East Asia, and Europe, the air quality community is preparing for an integrated global atmospheric composition observing system at unprecedented spatial and temporal resolutions. One of the ways that NASA has supported this community preparation is through demonstration of future space-borne capabilities using the Geostationary Trace gas and Aerosol Sensor Optimization (GeoTASO) airborne instrument. This paper integrates repeated high-resolution maps from GeoTASO, ground-based Pandora spectrometers, and low Earth orbit measurements from the Ozone Mapping and Profiler Suite (OMPS), for case studies over two metropolitan areas: Seoul, South Korea on June 9th, 2016 and Los Angeles, California on June 27th, 2017. This dataset provides a unique opportunity to illustrate how geostationary air quality monitoring platforms and ground-based remote sensing networks will close the current spatiotemporal observation gap. GeoTASO observes large differences in diurnal behavior between these urban areas, with NO2 accumulating within the Seoul Metropolitan Area through the day but NO2 peaking in the morning and decreasing throughout the afternoon in the Los Angeles Basin. In both areas, the earliest morning maps exhibit spatial patterns similar to emission source areas (e.g., urbanized valleys, roadways, major airports). These spatial patterns change later in the day due to boundary layer dynamics, horizontal transport, and chemistry. The nominal resolution of GeoTASO is finer than will be obtained from geostationary platforms, but when NO2 data over Los Angeles are up-scaled to the expected resolution of TEMPO, spatial features discussed are conserved. Pandora instruments installed in both metropolitan areas capture the diurnal patterns observed by GeoTASO, continuously and over longer time periods, and will play a critical role in validation of the next generation of satellite measurement.. These case studies demonstrate that different regions can have diverse diurnal patterns and that day-to-day variability due to meteorology or anthropogenic patterns such as weekday/weekend variations in emissions is large. Low Earth orbit measurements, despite their inability to capture the diurnal patterns at fine spatial resolution, will be essential for intercalibrating the geostationary radiances and cross-validating the geostationary retrievals in an integrated global observing system.

Dataset Information

Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.

Publications

Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.

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