Various DNA alterations can be caused by exposure to environmental and endogenous carcinogens. Most of these alterations, if not repaired, can result in genetic instability, mutagenesis and cell death. DNA repair mechanisms are important for maintaining DNA integrity and preventing carcinogenesis. Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We identified a sufficient number of epidemiologic studies on lung cancer to conduct a meta-analysis for genetic polymorphisms in nucleotide excision repair pathway genes, focusing on xeroderma pigmentosum group A (XPA), excision repair cross complementing group 1 (ERCC1), ERCC2/XPD, ERCC4/XPF and ERCC5/XPG. We found an increased risk of lung cancer among subjects carrying the ERCC2 751Gln/Gln genotype (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.14 - 1.49). We found a protective effect of the XPA 23G/G genotype (OR = 0.75, 95% CI = 0.59 - 0.95). Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples.

Consumption of caffeine-rich beverages, which have diuretic properties, may decrease serum uric acid concentrations. We examined cross-sectionally the relationship of coffee and green tea consumption to serum uric acid concentrations in 2240 male self-defence officials who received a pre-retirement health examination at four hospitals of the Self-Defence Forces between 1993 and 1994. The mean levels of coffee and green tea consumption were 2·3 and 3·1 cups/d respectively. There was a clear inverse relationship between coffee consumption and serum uric acid concentration. When adjusted for hospital only, those consuming less than one cup of coffee daily had a mean serum uric acid concentration of 60 mg/l, while that of those drinking five or more cups of coffee daily was 56 mg/l (P < 0·0001). No such relationship was observed for green tea, another major dietary source of caffeine in Japan. The relationship between coffee consumption and serum uric acid concentration was independent of age, rank in the Self-Defence Forces, BMI, systolic blood pressure, serum creatinine, serum total cholesterol and serum HDL-cholesterol concentrations, smoking status, alcohol use, beer consumption and intake of dairy products. These findings suggest that coffee drinking may be associated with lower concentrations of serum uric acid, and further studies are needed to confirm the association.

A functional polymorphism in the promoter region of the 5-hydroxytryptamine (serotonin) transporter (5-HTT) gene, termed 5-HTTLPR, alters transcription of the 5-HTT gene. The short variation (S allele) produces less transcriptional efficiency of serotonin, which can partly account for psychiatric disorders. Despite strong biological plausibility, the relationship between 5-HTTLPR and the risk of major depressive disorder (MDD) is unclear. To elucidate the relationship, we applied meta-analysis techniques to molecular studies of 5-HTTLPR and MDD. A total of 22 articles were identified from MEDLINE through March 2008, using the search keywords ‘depression,’ ‘5-HTTLPR’, and ‘polymorphism.’ The authors assessed the evidence of genotypic association using STATA Version 8.2. Summary frequencies of the S allele of 5-HTTLPR among Caucasians and Asians based on the random effects model were 42.1% [95% confidence interval (CI) = 40.5–43.6] and 76.8% (95% CI = 73.9–79.7), respectively. The distribution of the S allele was significantly different between Asians and Caucasians (P<0.001). The SS genotype was significantly associated with an increased risk of MDD among Caucasian populations (odds ratio = 1.41, 95% CI = 1.15–1.72), although there was no significant association among Asians. Although the summary risk for developing MDD in individuals with the ‘at-risk’ SS genotype of 5-HTTLPR may be small, MDD is such a common disease that even a small increase in risk translates to a large number of excess MDD cases in the population. Thus, 5-HTT may be a candidate MDD susceptibility gene.