Genetic variation in five genes important in telomere biology and risk for breast cancer

Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (−1381C>T, −244C>T, and Ex2-659G>A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53–1.00, 0.46–0.95 and 0.39–0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies

Respiratory tract mortality in cement workers: a proportionate mortality study

Background: The evidence regarding the association between lung cancer and occupational exposure to cement is controversial. This study investigated causes of deaths from cancer of respiratory tract among cement workers. Methods: The deaths of the Greek Cement Workers Compensation Scheme were analyzed covering the period 1969-1998. All respiratory, lung, laryngeal and urinary bladder cancer proportionate mortality were calculated for cement production, maintenance, and office workers in the cement industry. Mortality from urinary bladder cancer was used as an indirect indicator of the confounding effect of smoking. Results: Mortality from all respiratory cancer was significantly increased in cement production workers (PMR = 1.91; 95% CI 1.54 to 2.33). The proportionate mortality from lung cancer was significantly elevated (PMR = 2.05; 95% CI 1.65 to 2.52). A statistically significant increase in proportionate mortality due to respiratory (PMR = 1.7; 95% CI 1.2 to 2.34). and lung cancer (PMR = 1.67; 95% CI = 1.15-2.34) among maintenance workers has been observed. The PMR among the three groups of workers (production, maintenance, office) did differ significantly for lung cancer (p = 0.001), while the PMR for urinary bladder cancer found to be similar among the three groups of cement workers. Conclusion: Cement production, and maintenance workers presented increased lung and respiratory cancer proportionate mortality, and this finding probably cannot be explained by the confounding effect of smoking alone. Further research including use of prospective cohort studies is needed in order to establish a causal association between occupational exposure to cement and risk of lung cancer

Occupation and risk of lung cancer in Central and Eastern Europe: the IARC multi-center case-control study.

OBJECTIVE: We sought to evaluate the role of occupation and industry in lung carcinogenesis in six countries in Central and Eastern Europe. METHODS: This multi-center case-control study included 2,056 male and 576 female lung cancer incidence cases diagnosed from 1998 to 2001 and 2,144 male and 727 female controls frequency-matched for sex and age. Unconditional regression models were applied to calculate the odds ratios after controlling for potential confounders including age (5-year groups), study center (15 centers), and tobacco pack-years. RESULTS: Elevated odds ratios (ORs) were found for men employed as production workers (OR 1.45, 95% CI 1.22-1.72), bookkeepers and cashiers (1.81, 1.03-3.24), general farmers (1.67, 1.08-2.60), livestock workers (2.54, 1.09-5.88), miners (2.17, 1.47-3.23), toolmakers and metal patternmakers (2.56, 1.34-4.94), glass formers (2.55, 1.18-5.50), dockworkers, and freight handlers (1.49, 1.04-2.12). Industries with elevated risk among men included mining (1.75, 1.20-2.57), manufacture of cement, lime, or plaster (3.62, 1.11-12.00), casting of metals (2.00, 1.17-3.45), manufacture of electric motors (2.18, 1.24-3.86). For women, elevated ORs were found for medical, dental, veterinary doctors (2.54, 1.01-6.31), librarians and curators (7.03, 1.80-27.80), sewers 3.63 (1.12-10.23). CONCLUSIONS: This study identifies new areas for further, explanatory analyses, especially in production work, and indicates new possible sources of exposure to cancer risk for women