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Molecular epidemiology is poised to make ever-greater contributions to understanding the genetic and environmental causes of human disease. Both agnostic and hypothesis-driven approaches to both categories of risk factors could lead to leaps in our understanding. Investment in new methods and approaches will be needed, however. Strong links between population scientists, bench scientists, bioinformaticians and engineers must also be fo rged if progress is to be made.

Background: Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants. Methods: We pooled 11 studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar 32P-postlabeling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, and season of blood collection, and a limited set of gene variants. Results: Lowest DNA adduct levels (P = 0.006) were observed in the spring (median = 0.50 adducts per 108 nucleotides), followed by summer (0.64), autumn (0.70), and winter (0.85). The same pattern emerged in multivariate analysis but only among never smokers (P = 0.02). Adduct levels were significantly lower (P = 0.001) in northern Europe (the Netherlands and Denmark; mean = 0.60, median = 0.40) than in southern Europe (Italy, Spain, France, and Greece; mean = 0.79, median = 0.60). Conclusions: In this large pooled analysis, we have found only weak associations between bulky DNA adducts and exposure variables. Seasonality (with higher adducts levels in winter) and air pollution may partly explain some of the interarea differences (north vs. south Europe), but most inter-area and interindividual variations in adduct levels still remain unexplained. Impact: Our study describes the largest pooled analysis of bulky DNA adducts so far, showing that interindividual variation is still largely unexplained, though seasonality seems to play a role. Cancer Epidemiol Biomarkers Prev; 19(12); 3174–81. ©2010 AACR.

In a broad sense, molecular epidemiology is the axis that unites insights at the molecular level and understanding of disease at the population level. It is also a partnership between epidemiologists and laboratory scientists in which investigations are conducted using the principles of both disciplines. A key trait of molecular epidemiology is to evaluate and establish the relationship between a biomarker and important exogenous and endogenous exposures, susceptibility, or disease, providing understanding that can be used in future research and public health and clinical practice. When potential solutions or interventions are identified, molecular epidemiology is also useful in developing and conducting clinical and intervention trials. It can then contribute to the translation of biomedical research into practical public health and clinical applications by addressing the medical and population implications of molecular phenomena in terms of reducing risk of disease. This chapter summarizes the contributions and research endeavours of molecular epidemiology and how they link with public health initiatives and clinical practice.

Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies. In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association was detected. The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years. European Union (FOOD-CT-2005-513943) (WP4-8) to Environmental Cancer Risk, nutrition and individual susceptibility Network of Excellence (EC CONTRACT Food-CT-2005-513943).

On 15-16 September 1997, the U.S. Environmental Protection Agency sponsored the Conference on Preventable Causes of Cancer in Children. The conference was convened to examine rising trends in reported incidence of childhood cancer and the association of these trends with environmental exposures. This paper summarizes recommendations for future research offered by participants. These recommendations included more collaborative research integrating epidemiology, molecular biology, toxicology, and risk assessment; the development of better protocols for toxicologic testing including carcinogenicity using young animals; and research focused on specific periods of development during which susceptibility to environmental agents may be enhanced. Also recommended was enhanced use and development of molecular biomarkers for identification of susceptible populations, and documentation of exposures and effects in epidemiologic and toxicologic studies. Although toxicologic testing is considered essential to determine the effects of potential carcinogens on biological organisms, participants emphasized the need to link these findings with epidemiologic and exposure assessment research.

The biological mechanisms responsible for the onset and exacerbation of asthma symptoms in children may involve the epigenetic regulation of inflammatory genes after environmental exposures. Using buccal cells, we hypothesized that DNA methylation in promoter regions of two asthma genes, inducible nitric oxide synthase (iNOS) and interferon γ (IFNγ), can vary over several days. Repeat buccal samples were collected 4 to 7 days apart from 34 children participating in the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study. Several field duplicates (sequential collection of two samples in the field) and replicates (one sample pyrosequenced twice) also were collected to ensure consistency with collection and laboratory procedures. DNA methylation was assessed by pyrosequencing a PCR of bisulfite-treated DNA. We found that replicate and field duplicate samples were correlated strongly (r = 0.86 to 0.99, P < 0.05), while repeat samples demonstrated low within-subject correlations (r = 0.19 to 0.56, P = 0.06 to 0.30). Our data reveal DNA methylation as a dynamic epigenetic mechanism that can be accessed safely and reproducibly in an inner city pediatric cohort using non-invasive buccal swabs and pyrosequencing technology.