Leukocyte DNA methylation and colorectal cancer among male smokers.

AIM: To explore the association between methylation in leukocyte DNA and colorectal cancer (CRC) risk in male smokers using the α-tocopherol, ß-carotene cancer prevention study. METHODS: About 221 incident CRC cases, and 219 controls, frequency-matched on age and smoking intensity were included. DNA methylation of 1505 CpG sites selected from 807 genes were evaluated using Illumina GoldenGate Methylation Cancer Panel I in pre-diagnostic blood leukocytes of study subjects. Tertiles of methylation level classified according to the distribution in controls for each CpG site were used to analyze the association between methylation level and CRC risk with logistic regression. The time between blood draw to cancer diagnosis (classifying cases according to latency) was incorporated in further analyses using proportional odds regression. RESULTS: We found that methylation changes of 31 CpG sites were associated with CRC risk at P < 0.01 level. Though none of these 31 sites remained statistically significant after Bonferroni correction, the most statistically significant CpG site associated with CRC risk achieved a P value of 1.0 × 10(-4). The CpG site is located in DSP gene, and the risk estimate was 1.52 (95% CI: 0.91-2.53) and 2.62 (95% CI: 1.65-4.17) for the second and third tertile comparing with the lowest tertile respectively. Taking the latency information into account strengthened some associations, suggesting that the methylation levels of corresponding sites might change over time with tumor progression. CONCLUSION: The results suggest that the methylation level of some genes were associated with cancer susceptibility and some were related to tumor development over time. Further studies are warranted to confirm and refine our results.

Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2.

To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.

Personal use of hair dye and cancer risk in a prospective cohort of Chinese women.

Although widely studied over the past 40 years, personal use of hair dye generally has not been associated with overall cancer risk. The association between hair dye use and risk of bladder and hematopoietic cancers has been less conclusive. Most hair dye studies have been case-control studies conducted in Caucasian populations. We examined the relationship between personal hair dye use and cancer risk in a prospective cohort of 70,366 Chinese women. After an average of 7 years of follow up, 2437 women were newly diagnosed with cancer by 31 December 2005. Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) of cancer risk associated with hair dye use, adjusting for potential confounding factors. Compared with women who reported no hair dye use, ever users had an overall cancer risk of 0.89 (95% CI 0.82, 0.97). No significant association was observed for several common cancers, including cancers of the breast (RR 0.93, 95% CI 0.78, 1.09), lung (RR 0.81, 95% CI 0.62, 1.09), stomach (RR 0.90, 95% CI 0.66, 1.21), and colorectum (RR 1.04, 95% CI 0.84, 1.28). We also found no significant association with most other cancers, including bladder cancer (RR 1.14, 95% CI 0.56, 2.35) and hematopoietic cancers overall (RR 0.89, 95% CI 0.59, 1.35) or their subtypes, including non-Hodgkin lymphoma, multiple myeloma, and leukemia. We generally found no evidence of an association between personal use of hair dye and cancer risk, although our study is limited by small numbers for certain cancer types.

Neighboring-nucleotide effects on the mutation patterns of the rice genome.

DNA composition dynamics across genomes of diverse taxonomy is a major subject of genome analyses. DNA composition changes are characteristics of both replication and repair machineries. We investigated 3,611,007 single nucleotide polymorphisms (SNPs) generated by comparing two sequenced rice genomes from distant inbred lines (subspecies), including those from 242,811 introns and 45,462 protein-coding sequences (CDSs). Neighboring-nucleotide effects (NNEs) of these SNPs are diverse, depending on structural content-based classifications (genome-wide, intronic, and CDS) and sequence context-based categories (A/C, A/G, A/T, C/G, C/T, and G/T substitutions) of the analyzed SNPs. Strong and evident NNEs and nucleotide proportion biases surrounding the analyzed SNPs were observed in 1-3 bp sequences on both sides of an SNP. Strong biases were observed around neighboring nucleotides of protein-coding SNPs, which exhibit a periodicity of three in nucleotide content, constrained by a combined effect of codon-related rules and DNA repair mechanisms. Unlike a previous finding in the human genome, we found negative correlation between GC contents of chromosomes and the magnitude of corresponding bias of nucleotide C at -1 site and G at +1 site. These results will further our understanding of the mutation mechanism in rice as well as its evolutionary implications.