The substantial decreases in CVD mortality over the last decades have overcome the impact of the growth and ageing of populations in the overall number of deaths, while stabilization in the number of cancer deaths was observed only in some of the high-income countries.
Chromosomal rearrangements, including translocations, require formation and joining of DNA double strand breaks (DSBs). These events disrupt the integrity of the genome and are frequently involved in producing leukemias, lymphomas and sarcomas. Despite the importance of these events, current understanding of their genesis is limited. To examine the origins of chromosomal rearrangements we developed Translocation Capture Sequencing (TC-Seq), a method to document chromosomal rearrangements genome-wide, in primary cells. We examined over 180,000 rearrangements obtained from 400 million B lymphocytes, revealing that proximity between DSBs, transcriptional activity and chromosome territories are key determinants of genome rearrangement. Specifically, rearrangements tend to occur in cis and to transcribed genes. Finally, we find that activation-induced cytidine deaminase (AID) induces the rearrangement of many genes found as translocation partners in mature B cell lymphoma.Copyright © 2011 Elsevier Inc. All rights reserved. PMID: 21962510 Funding information This work was supported by: NIGMS NIH HHS, United States Grant ID: T32 GM007739 NIAID NIH HHS, United States Grant ID: R37 AI037526 NIAID NIH HHS, United States Grant ID: AI037526 Howard Hughes Medical Institute, United States NIAID NIH HHS, United States Grant ID: R01 AI037526-17 Intramural NIH HHS, United States NIGMS NIH HHS, United States Grant ID: GM07739 NIAID NIH HHS, United States Grant ID: R01 AI037526 More Less keyboard_arrow_down
We thank Drs. Franceschi and Vaccarella1 for their interest in our work, and for the additional comments and insights they provided on the recent apparent epidemic of early papillary thyroid cancers.2 The choice of the scales in figures of trends in rates in different countries remains arbitrary. The use of different scales for various countries optimizes the within-country information, whereas the use of a single scale for all countries optimizes the between-country comparison; however, it makes difficult to investigate country-specific trends, in particular for those with low rates. A key observation by Drs. Franceschi and Vaccarella is that the rise in female thyroid cancer incidence over the last two decades has been largely heterogeneous across selected high-income countries providing data, and that there are at least three countries (Denmark, UK and Japan) where the rise has been modest in absolute terms—though not in relative ones—as indicated in Figure 5. Such a moderate rise has already been observed in selected well-surveilled populations.3 Drs. Franceschi and Vaccarella attributed the relatively modest absolute rise in thyroid cancer incidence in Denmark, UK and Japan to different organization in their health systems and in their utilization of innovative diagnostic practices, although the quantification of the role of these factors remains elusive. We agree with Drs. Franceschi and Vaccarella that overdiagnosis of thyroid cancer can have serious long-term consequences, and that more conservative approaches to the management of low-risk thyroid cancers are required. We also agree that the implementation of randomized clinical trials on such management would assist in providing evidence-based indications. The authors thank Mrs I. Garimoldi for editorial assistance.
On the basis of clinical observations that some women with fibrocystic breast disease experienced resolution of the disease on eliminating methylxanthines from their diet, it has been suggested that coffee intake might be related to breast carcinogenesis. The relationship between coffee (mostly expresso and mocha), decaffeinated coffee and tea intake and breast cancer risk was therefore considered, combining data from two case-control studies, conducted in Italy between 1983 and 1994. Cases were 5,984 women, below age 75, with histologically confirmed breast cancer, and controls were 5,504 women admitted to hospital for a wide spectrum of acute, non-neoplastic, non-hormone-related diseases. The odds ratios (ORs) were estimated from multiple logistic regression equations including terms for study/centre, age, education, body mass index, smoking status, total alcohol intake, age at menarche and menopause, parity and age at first birth, use of oral contraceptives, use of hormone replacement therapy, history of benign breast disease and family history of breast cancer. No relationship was observed between coffee intake and the risk of breast cancer. The multivariate ORs were 1.17 (1.03-1.33), 1.17 (1.04-1.33), 1.21 (1.06-1.37) and 0.96 (0.83-1.11) for women drinking < 2, 2, > 2 to < 4 and > or = 4 cups/day compared to non-drinkers. Decaffeinated coffee was consumed only by 6-7% of cases and controls and the corresponding OR was 0.84 (0.72-0.98). Tea consumption was also low and not associated with the risk of breast cancer (OR 0.94, 95% CI 0.85-1.03). No significant heterogeneity was found for coffee intake across strata of age at diagnosis, education, body mass index, smoking status, total alcohol intake, age at menarche and menopause, parity, age at first birth, ever use of oral contraceptives, hormone replacement therapy, history of benign breast disease and family history of breast cancer. Thus, this study, based on a large data set, allows us to exclude the hypothesis that coffee intake is related to breast cancer risk in this Italian population.
A population-based case-control study of gallbladder cancer was conducted in the south-west of Poland, within the frame-work of the SEARCH Programme of the International Agency for Research on Cancer. A total of 73 cases and 186 controls were interviewed using a questionnaire including demographic and socio-economic factors, education, smoking, alcohol, tea and coffee consumption, and past medical history. A validated diet history was used to estimate the daily intake of calories, fats, carbohydrates, proteins, cholesterol, fibres and vitamins C and E. Gallbladder disease was the major determinant of subsequent gallbladder cancer: 41 cases (56%) vs. 15 (8%) controls had a past history of gallbladder disease, corresponding to an odds ratio (OR) of 12.5 (95% confidence interval, 5.8 to 26.6), and the OR was 12.1 for gallbladder problems dating back 20 years or more in the past. There was an inverse relationship with education, the OR being 0.3 (95% CI 0.1 to 1.2) for 13 years of education or more vs. less than 7. Gallbladder cancer risk was positively associated with total calorie intake, with ORs of 1.4, 1.5, 4.1 for the 3 upper quartiles compared with the lowest one (trend, p less than 0.01). Weaker direct associations were observed for proteins, carbohydrates and cholesterol. There was some suggestion of inverse associations with fibre intake, and a more consistent one with vitamins C and E. These results further quantify the role of gallstones, and suggest that total calorie intake and other dietary factors potentially linked with benign gallbladder conditions are involved in the aetiology of gallbladder cancer.
Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.
This short and essential book [1] is addressed essentially to medical and public health students, and to anyone interested in a summary up to date presentation of cancer epidemiology and prevention. It is subdivided into four major sections, that include principles of primary and secondary cancer prevention, the current global burden of neoplasms,...
