Non-Hodgkin lymphomas (NHL) are among the few neoplasms whose incidence and mortality have been rising in Europe and North America over the last few decades. To update trends from NHL, we considered mortality data up to 2004 in several European countries, and for comparative purpose in the USA and Japan. We also analyzed patterns in incidence for selected European countries providing national data. In most European countries, NHL mortality rose up to the mid 1990s, and started to level off or decline in the following decade. The rates were, however, still increasing in eastern Europe. Overall, in the European Union, mortality from NHL declined from 4.3/100,000 to 4.1 in men and from 2.7 to 2.5 in women between the late 1990s and the early 2000s. Similarly, NHL mortality rates declined from 6.5/100,000 to 5.5 in US men and from 4.2 to 3.5 in US women. In most countries considered, NHL incidence rates rose up to 1995-99, while they tended to level off or decline thereafter, with particular favorable patterns in countries from northern Europe. Thus, the epidemic of NHL observed during the second half of the 20th century has now started to level off in Europe as in other developed areas of the world.

False-positive results are inherent in the scientific process of testing hypotheses concerning the determinants of cancer and other human illnesses. Although much of what is known about the etiology of human cancers has arisen from well-conducted epidemiological studies, epidemiology has been increasingly criticized for producing findings that are often sensationalized in the media and fail to be upheld in subsequent studies. Herein we describe examples from cancer epidemiology of likely false-positive findings and discuss conditions under which such results may occur. We suggest general guidelines or principles, including the endorsement of editorial policies requiring the prominent listing of study caveats, which may help reduce the reporting of misleading results. Increased epistemological humility regarding findings in epidemiology would go a long way to diminishing the detrimental effects of false-positive results on the allocation of limited research resources, on the advancement of knowledge of the causes and prevention of cancer, and on the scientific reputation of epidemiology and would help to prevent oversimplified interpretations of results by the media and the public.

The incidence of contralateral breast cancer is high and constant with age, around five per 1000 women who had a primary breast cancer. For other neoplasms, the pattern of incidence of second primary neoplasms with age is less known, particularly as for only a few neoplasms the site of origin is not totally removed, and hence remains at risk of a second primary. Using the dataset from the Cancer Registry of the Swiss Canton of Vaud, we show that the incidence of second neoplasms is constant with age also after oral and pharyngeal, colorectal cancers, cutaneous malignant melanoma (CMM) and basal cell carcinoma. The incidence of first primary oral and pharyngeal cancer increased 20-fold between age 30-39 and 70-89 years, whereas the incidence of second neoplasms did not increase with age. Rates of second colorectal cancer remained relatively constant with age, between 2.5 per 1000 at age 40-59 years and 3.8 per 1000 at 70 years and above. Likewise, for CMM, the age-specific incidence rates of second primary CMM did not vary, ranging between 1 and 2.5 per 1000 in various subsequent age groups. The pattern of incidence for second basal cell carcinoma was similar, with no clear rise with age. These patterns are compatible with the occurrence of a single mutational event in a population of susceptible individuals. A possible implication of these observations is that a variable, but potentially large, proportion of cancers arise in very high-risk individuals and the incidence, on average, increases at a high constant level at a predetermined age.

Benign ovarian cysts have been suggested to influence breast cancer risk. To provide a comprehensive picture of the relation between ovarian cysts and breast cancer, we analyzed the data of 3 case-control studies conducted in northern Italy and the Swiss Canton of Vaud between 1983 and 2001. These studies included 6,315 incident, histologically confirmed breast cancer cases and 6,038 hospital-based controls. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models, including terms for sociodemographic, menstrual and reproductive factors. Overall, 4.9% of breast cancer cases and 6.6% of controls reported a history of ovarian cysts, with a multivariate OR of 0.72 (95% CI 0.62-0.85). The inverse association between ovarian cysts and breast cancer was consistent in separate strata of age at menarche, parity, age at menopause status and family history of breast cancer. No meaningful differences were also found across strata of menstrual cycle length, oral contraceptive use, history of oophorectomy and body mass index. Thus, the inverse relation between ovarian cysts and breast cancer risk was not accounted for by earlier menopause, or by any difference in reproductive and menstrual characteristics. Although some hormonal correlates of ovarian cysts may have a role on breast cancer risk, a biological explanation of this inverse association is still unclear.

We estimated the number of cancer cases and deaths attributable to alcohol drinking in 2002 by sex and WHO subregion, based on relative risks of cancers of the oral cavity, pharynx, esophagus, liver, colon, rectum, larynx and female breast obtained from recent meta- and pooled analyses and data on prevalence of drinkers obtained from the WHO Global Burden of Disease project. A total of 389,100 cases of cancer are attributable to alcohol drinking worldwide, representing 3.6% of all cancers (5.2% in men, 1.7% in women). The corresponding figure for mortality is 232,900 deaths (3.5% of all cancer deaths). This proportion is particularly high among men in Central and Eastern Europe. Among women, breast cancer comprises 60% of alcohol-attributable cancers. Although our estimates are based on simplified assumptions, the burden of alcohol-associated cancer appears to be substantial and needs to be considered when making public health recommendations on alcohol drinking.

To monitor recent trends in mortality from oesophageal cancer in 33 European countries, we analyzed the data provided by the World Health Organization over the last 2 decades, using also joinpoint regression. For selected European cancer registration areas, we also analyzed incidence rates for different histological types. For men in the European Union (EU), age-standardized (world population) mortality rates were stable around 6/100,000 between the early 1980s and the early 1990 s, and slightly declined in the last decade (5.4/100,000 in the early 2000s, annual percent change, APC = -1.1%). In several western European countries, male rates have started to level off or decline during the last decade (APC = -3.4% in France, and -3.0% in Italy). Also in Spain and the UK, which showed upward trends in the 1990 s, the rates tended to level off in most recent years. A levelling of rates was observed only more recently in countries of central and eastern Europe, which had had substantial rises up to the late 1990 s. Oesophageal cancer mortality rates remained comparatively low in European women, and overall EU female rates were stable around 1.1-1.2/100,000 over the last 2 decades (APC = -0.1%). In northern Europe a clear upward trend was observed in the incidence of oesophageal adenocarcinoma, and in Denmark and Scotland incidence of adenocarcinoma in men is now higher than that of squamous-cell carcinoma. Squamous-cell carcinoma remained the prevalent histological type in southern Europe. Changes in smoking habits and alcohol drinking for men, and perhaps nutrition, diet and physical activity for both sexes, can partly or largely explain these trends.

Although tobacco smoking has long been recognized as a major risk factor for cancer of the upper aero-digestive tract (UADT, i.e., oral cavity, pharynx, larynx, and oesophagus), very few studies have provided estimates of the effect of very low tobacco consumption. Step-functions have been the common statistical methods for risk estimates, but the choice of reference category and of interval cutpoints influence the results, especially when data are sparse. In the present analysis, the dose-response relationship between UADT cancers and tobacco smoking was evaluated through logistic regression spline models. We included 1,241 UADT male cases and 2,835 male controls pooled from a large series of case-control studies conducted in northern Italy and in the Swiss Canton of Vaud during the last 2 decades. For cancers of the pharynx, larynx and oesophagus, the risk steadily increased with number of cigarettes/day. The risk of oral, pharyngeal and oesophageal cancers was significantly higher in smokers than in nonsmokers beginning with as low as 2 cigarettes/day. The effect of tobacco smoking at low levels seemed less evident for laryngeal cancer since the raise in risk begun with 6 cigarettes/day. In conclusion, for all the examined UADT sites, a monotonic dose-response relationship between cancer risk and cigarette smoking emerged. The excess of risk among people smoking 2 cigarettes/day highlights the absence of any harmless level for cigarette smoking, and it further supports the need of public health programs against tobacco smoking.