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A recent systematic review and meta-analysis of studies on physical activity and pancreatic cancer,1 based on 22 prospective and six case-control investigations, reported no strong evidence for association. There was a modest inverse association with total and occupational physical activity, recreational activity showed inconsistent relations, whereas no association was found with high intensity activity. Several aspects of physical activity, including the role of activity in early life, have been scarcely considered to date.2 To provide further information on the issue, we analyzed data on physical activity in a case-control study of pancreatic cancer conducted in two areas of Northern Italy. The characteristics of this study have been described elsewhere.3 Briefly, cases were 326 patients (174 men and 152 women, median age 63 years) with histologically confirmed incident cancer of the pancreas, admitted to the major teaching and general hospitals in the study areas, and with no previous cancer diagnosis. Histologically confirmed neuroendocrine tumors of the pancreas were excluded. Controls were 652 patients (348 men and 304 women, median age 63 years) admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, unrelated to smoking, alcohol consumption, or long-term modifications of diet. Controls were frequency-matched to cases by sex, age, and study center. For both cases and controls, data were collected during the hospital stay by trained interviewers using a standardized, structured questionnaire. The section on physical activity included questions on self-reported intensity of activity at work and during leisure time separately, in different periods of life. For occupational physical activity, patients were asked whether their jobs were “very heavy,” “heavy,” “average,” “standing,” or “mainly sitting,” according to a structured scale classified into five categories. Physical activity during leisure time was defined on the basis of the number of hours per week of sport or activity, such as walking, gardening, cycling, etc. Scores ranged between 1 and 4, corresponding respectively to <2, 2–4, 5–7, and >7 hours of physical activity per week. The scores of the two lowest and the two highest levels of occupational physical activity and the scores of the two highest levels of recreational physical activity were combined together, since there were too few subjects in these categories. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were derived using conditional multiple logistic regression. All regression models were stratified on age, sex, and study center, and adjusted for year of interview, education, smoking habit, alcohol drinking, diabetes, body mass index, and energy intake. Table 1 shows the distribution of cases and controls and the corresponding ORs and 95% CI according to occupational and recreational physical activity at various ages. For the highest vs. the lowest level of occupational physical activity, the ORs were 1.24 (95% CI, 0.79–1.95) at age 15–19, 1.21 (95% CI, 0.80–1.85) at age 30–39 and 1.41 (95% CI, 0.90–2.22) at age 50–59, with no significant trend in risk at any age considered. The corresponding ORs for recreational physical activity were 1.44 (95% CI, 0.97–2.13) at age 15–19, 1.52 (95% CI, 1.03–2.24) at age 30–39 and 1.39 (95% CI, 0.91–2.14) at age 50–59. A significant positive trend in risk emerged only for recreational physical activity at age 30–39 (p = 0.02). Therefore, occupational and recreational physical activity were not associated to a decreased risk of pancreatic cancer in our study. Results for physical activity during the teenage period were comparable to those at older ages, indicating a lack of association or, if any, a modest increase in risk of pancreatic cancer for high recreational physical activity in early life. Previous case-control studies were conducted in North America and generally reported inconsistent results. In a Canadian study,4 men with the highest index of total physical activity had an almost halved risk of pancreatic cancer as compared to those in the lowest level, whereas no association was found in women. A study from the San Francisco Bay area5 found a nonsignificant roughly 20% decreased risk in both sexes for subjects with high activity level as compared to inactive ones. A recent investigation from the Upper Midwest of the United States6 reported a decreased pancreatic cancer risk associated to physical activity; however, this association was limited to light and moderate activity, in the absence of any trend in risk. However, a study conducted in Missouri7 showed that men with moderate occupational activity level had a slightly increased risk of pancreatic cancer as compared to those with both high and low levels of occupational activity. In conclusion, our data do not indicate a major role of physical activity on pancreatic cancer risk. Although our point estimates of risk were somewhat higher as compared with previous investigations, the results were in broad agreement with other reports when considering the whole range of the CIs. The evidence from cohort and case-control studies, therefore, weighs against a relevant role of physical activity in pancreatic cancer risk. Claudio Pelucchi*, Antonella Zucchetto , Alessandra Tavani*, Luigino Dal Maso , Diego Serraino , Carlo La Vecchia* , * Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, Struttura Operativa Complessa di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (PN), Italy, Dipartimento di Medicina del Lavoro, Clinica del Lavoro Luigi Devoto, Sezione di Statistica Medica e Biometria Giulio, A. Maccacaro, Università degli Studi di Milano, Milan, Italy.
Abstract Neoplasms continue to dominate globally as one of the major sources of human disease and death. There are multiple modifiable causes of cancer and understanding their attributable risk factors for each cancer is of importance. This chapter covers the role of cellular and molecular mechanisms as well as the experimental and epidemiological approaches as determinants of the main cancers. Even if major discoveries in the clinical management of cancer patients will be accomplished in the near future, the changes will mainly affect the affluent part of the world population. Promising approaches focused on prevention of the known causes, reducing its consequences, notably in resource-constrained settings are highlighted.
The protection conveyed by oral contraceptives against ovarian cancer risk is one of the best established and most important features of epithelial ovarian cancer on a public health scale. Ovarian cancer incidence and mortality rates have been declining in most developed countries for women born after 1920, and the decline was greater in countries where oral contraceptive use has been more widespread. Thus, data from descriptive epidemiology are consistent with a favourable effect of oral contraceptives on ovarian cancer risks. The overall estimated protection from cohort and case-control studies is approximately 40% in ever oral contraceptive users, and increases with duration of use to more than 50% for users of 5 years or longer. The favourable effect of oral contraceptives against ovarian cancer risk persists for at least 10-15 years after use has ceased, and it is not confined to any particular type of oral contraceptive formulation. However, available data do not provide definite evidence for more recent low-dose formulations and for longer periods of latency or recency of use. The protection is also observed on borderline malignancy ovarian neoplasms, and probably on benign epithelial cysts as well. There is suggestive evidence of some protection for sex-cord-stromal cancers, but not for germ cell neoplasms. In terms of biological mechanisms, oral contraceptives are thought to act on ovarian cancer risk by affecting the lifetime number of ovulations. The protection attributable to oral contraceptives on ovarian cancer risk is one of the major issues on any individual risk/benefit assessment and public health evaluation of this type of contraceptive use.
