A B S T R A C T PurposeChronic inflammation could play a role in lung carcinogenesis, underscoring the potential for lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP, an inflammation biomarker) and CRP single nucleotide polymorphisms (SNPs) with prospective lung cancer risk. Patients and MethodsWe conducted a nested case-control study of 592 lung cancer patients and 670 controls with available prediagnostic serum and 378 patients and 447 controls with DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N ϭ 77,464). Controls were matched to patients on age, sex, entry year, follow-up time, and smoking. We measured CRP levels in baseline serum samples and genotyped five common CRP SNPs. ResultsElevated CRP levels were associated with increased lung cancer risk (odds ratio [OR], 1.98; 95% CI, 1.35 to 2.89; P-trend Ͻ .001 for fourth quartile [Q4, Ն 5.6 mg/L] v Q1 [Ͻ 1.0 mg/L]). The CRP association did not differ significantly by histology, follow-up time, or smoking status, but was most apparent for squamous cell carcinomas (OR, 2.92; 95% CI, 1.30 to 6.54), 2 to 5 years before lung cancer diagnosis (OR, 2.33; 95% CI, 1.24 to 4.39), and among former smokers (OR, 2.48; 95% CI, 1.53 to 4.03) and current smokers (OR, 1.90; 95% CI, 1.06 to 3.41). Although CRP SNPs and haplotypes were associated with CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels among former smokers (Q4: 2.55%; 95% CI, 1.98% to 3.27% v Q1: 1.39%; 95% CI, 1.07% to 1.81%) and current smokers (Q4: 7.37%; 95% CI, 5.81% to 9.33% v Q1: 4.03%; 95% CI, 3.01% to 5.40%). ConclusionElevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis.
"The distribution of population and employment in metropolitan Los Angeles in 1970 and 1980 is examined in this paper. Population continued to disperse in the 1970s, whereas the geographical distribution of employment combined job clustering around a few major employment centers with a high degree of general job dispersion. In Los Angeles polycentrism has been associated with shorter work trips, particularly intracounty trips in the more peripheral counties." Population data are for 2,403 comparable census tracts for 1970 and 1980; data concerning geographical employment distribution are from the 1980 census.
Vitamin D has been implicated as a protective agent against colorectal cancer. We hypothesized that a functional start codon polymorphism in the vitamin D receptor (VDR) influences the risk of colorectal carcinoma. We conducted a case-control study nested within a large cohort of Singapore Chinese. VDR genotypes, determined by FokI restriction endonuclease digestion of PCR-amplified DNA, were performed on 217 colorectal cancer cases and 890 controls. We found that compared with individuals carrying the FF genotype, those with Ff genotype had a 51% increase in risk of colorectal cancer and those with the ff genotype, an 84% increase in risk (P for trend = 0.01). The effect of the VDR genotype on risk appeared to be modified by both dietary calcium and fat. Among those with either low calcium or low fat intake (below the median values in controls), the risk for colorectal cancer increased in a gene-dose-dependent manner such that individuals possessing the ff genotype displayed an approximately 2.5-fold increased risk that was statistically significant. There was little evidence of a VDR genotype-colorectal cancer association among subjects with higher than median values of either dietary fat or calcium.
Loss of imprinting (LOI) is a common epigenetic event in cancer and may serve as an early biomarker in some cancers. To obtain a better understanding of LOI, we studied 41 bladder tumors and their adjacent normal bladder mucosa. We found 2/9 (22.2%) cases that displayed LOI of IGF2 and 2/16 (12.5%) that had LOI of H19, as determined by the evaluation of mRNA for biallelic expression. In addition, we examined allele-specific methylation of the differentially methylated regions (DMR) of IGF2 and H19 using a new allele-specific pyrosequencing assay. We found that DNA methylation changes were a common finding (21/30, 70%) in the DMR regions, but could not clearly link DNA methylation changes with LOI as measured by biallelic expression. LOI and allele-specific DNA methylation changes are present in bladder cancer; however, a better understanding of the biology of LOI and its relationship to DNA methylation changes is needed before its use as an epigenetic biomarker. [Cancer Res 2007;67(22):10753-8]
A large national sample from the US 1977 Nationwide Personal Transportation Study is analyzed in order to test the transport economies that may result from the dispersion of work trip-ends. Based on indirect evidence that the largest metropolitan areas have the largest proportion of noncentral-city work trip-ends, we associate a variety of work-trip results for such cities with a polycentric urban form hypothesis. We claim that these results also suggest that decentralized settlement (‘sprawl’?) is not necessarily uneconomical.
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