A growing number of well-designed epidemiological and molecular studies provide substantial evidence that the pesticides used in agricultural, commercial, and home and garden applications are associated with excess cancer risk. This risk is associated both with those applying the pesticide and, under some conditions, those who are simply bystanders to the application. In this article, the epidemiological, molecular biology, and toxicological evidence emerging from recent literature assessing the link between specific pesticides and several cancers including prostate cancer, non-Hodgkin lymphoma, leukemia, multiple myeloma, and breast cancer are integrated. Although the review is not exhaustive in its scope or depth, the literature does strongly suggest that the public health problem is real. If we are to avoid the introduction of harmful chemicals into the environment in the future, the integrated efforts of molecular biology, pesticide toxicology, and epidemiology are needed to help identify the human carcinogens and thereby improve our understanding of human carcinogenicity and reduce cancer risk. CA Cancer J Clin 2013;63:120-142.

Our results indicate greater positional errors for rural addresses compared with town addresses. Using a commercial firm did not improve accuracy compared with our in-house method. The effect of geocoding errors on exposure classification will depend on the spatial variation of the exposure being studied.

Mitochondria are eukaryotic organelles responsible for energy production. Mitochondrial DNA (mtDNA) lack introns and protective histones, have limited DNA repair capacity and compensate for damage by increasing the number of mtDNA copies. As a consequence, mitochondria are more susceptible to reactive oxygen species, an important determinant of cancer risk, and it is hypothesized that increased mtDNA copy number may be associated with carcinogenesis. We assessed the association of mtDNA copy number and lung cancer risk in 227 prospectively collected cases and 227 matched controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age at randomization, smoking years and number of cigarettes smoked per day. There was suggestion of a dose-dependent relationship between mtDNA copy number and subsequent risk of lung cancer, with a prominent effect observed in the highest mtDNA copy number quartile [ORs (95% CI) by quartile: 1.0 (reference), 1.3 (0.7-2.5), 1.1 (0.6-2.2) and 2.4 (1.1-5.1); P(trend) = 0.008]. This is the first report, to the best of our knowledge, to suggest that mtDNA copy number may be positively associated with subsequent risk of lung cancer in a prospective cohort study; however, replication is needed in other studies and populations.

Objective We previously reported that total suspended particulates exposure (a measure of air pollution) at the time of birth was related to increased postmenopausal breast cancer risk. In this study, we examined breast cancer risk in relation to exposure to air pollution from traffic emissions throughout life. Methods We conducted a case-control study of breast cancer. Participants were women, aged 35-79, residents of Erie and Niagara Counties. Cases had incident, primary, histologically confirmed breast cancer. Controls were randomly selected from the population, frequency-matched on age and race. Using lifetime residential histories, exposure to traffic emissions was modeled for each woman using her residence as a proxy. Estimates were calculated for residence at menarche, her first birth, and 20 and 10 years before interview. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results Higher exposure to traffic emissions at the time of menarche was associated with increased risk of premenopausal breast cancer (OR 2.05, 95% CI 0.92-4.54, p for trend 0.03); and at the time of a woman's first birth for postmenopausal breast cancer (OR 2.57, 95% CI 1.16-5.69, p for trend 0.19). Statistically significant associations were limited to lifetime non-smokers; there was a significant interaction between exposure at time of menarche and smoking for premenopausal women. Conclusion Our findings add to accumulating evidence that early life exposures impact breast cancer risk and provide indication of potential importance of traffic emissions in risk of breast cancer.

The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR 5 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR 5 0.40, 95% CI 0.19-0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR 5 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs. ' 2005 Wiley-Liss, Inc.Key words: lung cancer; DNA repair; single nucleotide polymorphism; nucleotide excision repair; polycyclic aromatic hydrocarbon Lung cancer is the leading cause of death from cancer worldwide, with an estimated mortality in 2000 of 31.4 per 100,000 for men and 9.5 per 100,000 for women. 1 Overall, lung cancer incidence and mortality rates are higher for males than females, due largely to the higher prevalence of tobacco smoking among men. Compared to worldwide patterns and those in China, lung cancer has distinctive characteristics in rural Xuan Wei County, Yunnan Province, China. Lung cancer mortality in Xuan Wei has been reported to be 8 times the Chinese national average for women and 4 times that for men. 2 Although very few women smoke, the lung cancer mortality rates in Xuan Wei County were similar between men and women (27.7 and 25.3 per 100,000 for males and females, respectively). 2 This pattern has been attributed to burning smoky coal indoors for heating and cooking without adequate ventilation with high exposure time, particularly among women, accounting for >90% of lung cancer cases for both men and women. 2,3 When smoky coal is burned, the indoor air concentration of particulate matter and extractable organic matter may be as high as 24.4 and 17.6 mg/m 3 , 2 respectively, and the corresponding benzo[a]pyrene concentration, an indicator of carcinogenic PAHs, can reach as high as 19.3 lg/m 3 , 4 which is comparable to exposure levels experien...