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Although previous investigations have indicated a role for genetic factors in smoking initiation, the underlying genetic mechanisms are still unknown. In 2,339 adolescents from a Chinese Han population in the Wuhan Smoking Prevention Trial (Wuhan, China, 1998-1999), the authors explored the association of 57 genes in the dopamine pathway with smoking initiation. Using a conservative approach for declaring significance, positive findings were further examined in an independent sample of 603 Caucasian adolescents followed for up to 10 years as part of the Children's Health Study (Southern California, 1993-2009). The authors identified 1 single nucleotide polymorphism (rs2298122) in the calcyon neuron-specific vesicular protein gene (CALY) that was positively associated with smoking initiation in females (odds ratio = 2.21, 95% confidence interval: 1.49, 3.27; P = 8.4 × 10(-5)) in the Wuhan Smoking Prevention Trial cohort, and they replicated the association in females from the Children's Health Study cohort (hazard rate ratio = 2.05, 95% confidence interval: 1.27, 3.31; P = 0.003). These results suggest that the CALY gene may influence smoking initiation in adolescents, although the potential roles of underlying psychological characteristics that may be components of the smoking-initiation phenotype, such as impulsivity or novelty-seeking, remain to be explored.

Background: Multiple chromosome 8q24 genotypic variants are strongly implicated in several cancers. Recent genome-wide association studies of urinary bladder cancer report risk to be associated with the T allele of rs9642880 on 8q24 among individuals of European descent., Methods: We examined associations between bladder cancer risk and genotypes defined by rs9642880 and each of 8 additional 8q24 variants associated with risk of other cancers, in both high-risk non-Hispanic white and low-risk Chinese participants enrolled in a large population-based case-control study conducted in Los Angeles County and Shanghai., Results: We confirmed association of rs9642880 T with bladder cancer risk not only among non-Hispanic whites but also among Chinese participants [overall per-allele relative risk estimate 1.32 (95% CI, 1.16-1.50; P = 0.000024)]. Subgroup analyses suggested that effects of rs9642880 are largely confined to nonsmokers and former smokers, and may be particularly important in the etiology of noninvasive papillary tumors. There was little indication that 8q24 SNPs associated with other cancer types--rs7008482, rs7000448, rs6983561, rs6983267, rs13281615, rs13254738, or rs10090154--are associated with bladder cancer risk., Conclusions: Bladder cancer risk is associated specifically with variation in the discrete 8q24 region containing rs9642880. Factors other than rs9642880 genotypes seem to underlie differences in bladder cancer risk between non-Hispanic whites and Chinese., Impact: Characterization of functional consequences of genetic variation in the discrete region including rs9642880 is needed to understand biological basis of this bladder cancer-specific 8q24 association in these racial/ethnic groups characterized by both high and low risk of bladder cancer., (©2010 AACR.)

Recently, the first genome-wide association study of bladder cancer identified an association of genome-wide significance between single nucleotide polymorphism (SNP) rs715021 and urinary bladder cancer risk among European individuals. This SNP is in a haplotype block in linkage disequilibrium with the TP63 gene. We investigated the role of this SNP among 1,042 cases and 1,123 controls among non-Latino whites in Los Angeles County, CA and among Chinese in Shanghai, China. We confirmed an association between the A allele and bladder cancer risk [log-additive per A allele odds ratios (OR), 1.24; and 95% confidence intervals (95% CI), 1.02-1.52; P = 0.032] in Los Angeles County and a similar association in Shanghai (log-additive per A allele OR, 1.21; 95% CI, 0.98-1.49; P = 0.080). These estimates did not differ by study site, smoking status, or gender. However, the effects were greater in older individuals. Analysis within non-Latino whites, for whom we had histologic results, revealed that this association was restricted to low-risk tumors (OR, 1.49; 95% CI, 1.17-1.92; P = 0.002) and absent among high-risk tumors (OR, 1.03; 95% CI, 0.80-1.33; P = 0.790; heterogeneity, P = 0.019). A positive association (OR, 1.56; 95% CI, 0.93-2.62; P = 0.089) was only observed among high-risk tumors from individuals older than 56 years old (interaction, P = 0.045). Our results suggest that a TP63 gene variant may increase susceptibility for the development of urinary bladder tumors with low risk of progression.

The conventional method of detecting gene-environment interactions, the case-control analysis, suffers from low statistical power. In contrast, the case-only analysis/design can be powerful in certain scenarios, although violation of the assumption of independence between the genetic and environmental factors can greatly bias the results. As an alternative, Bayes model averaging may be used to combine the case-control and case-only analyses. This approach first frames the case-control and case-only analyses as variations of a log-linear model. The weighting between these 2 models is then a function of the data and prior beliefs on the independence of the 2 potentially interacting factors. In this paper, the authors demonstrate via simulations that when there is no prior information on the independence of the genetic and environmental factors, this approach tends to be more powerful than the case-control analysis. Additionally, when the genetic and environmental factors are not independent in the population, bias is substantially reduced, with a corresponding reduction in type I error in comparison with the case-only analysis. Increased power or increased robustness to violations of the independence assumption may be obtained with more appropriate prior specification. The authors use an example data analysis to demonstrate the advantages of this approach.

Purpose: This study examined the differences in smoking progression between middle and upper school students., Methods: The China Seven Cities Study (CSCS) is a longitudinal cohort study. The current sample consists of subjects with both baseline and one-year follow-up measures collected between October 2002 and December 2003. There were 4842 students from 62 middle schools and 5806 students from 83 upper schools. Multilevel random-coefficient modeling techniques were applied., Results: Among male never or lifetime ever smokers, middle school students were susceptible to transitioning more rapidly than upper school students (never--RR: 1.272, 95% confidence interval [CI]: .985-1.642; lifetime ever--RR: 1.497, 95% CI: .979-2.290). Among female lifetime ever smokers, middle school students were more likely to progress than upper school students (RR: 1.353, 95% CI: 1.038-1.763)., Conclusion: This longitudinal study is the first to explore differences in smoking progression among adolescents in China. The results revealed that over a one-year interval, there was greater progression across smoking trajectories during early adolescence (corresponding to middle school) than later adolescence (upper school). This is consistent with the neurological development hypothesis, but does not rule out alternative explanations. These findings are important to consider relative to the content and timing of prevention interventions in China where smoking rates approach 70% in adult males and are increasing rapidly in women.