To evaluate the strength of the evidence provided by the epidemiological literature on the association between alcohol consumption and the risk of 18 neoplasms, we performed a search of the epidemiological literature from 1966 to 2000 using several bibliographic databases. Meta-regression models were fitted considering linear and non-linear effects of alcohol intake. The effects of characteristics of the studies, of selected covariates (tobacco) and of the gender of individuals included in the studies, were also investigated as putative sources of heterogeneity of the estimates. A total of 235 studies including over 117 000 cases were considered. Strong trends in risk were observed for cancers of the oral cavity and pharynx, oesophagus and larynx. Less strong direct relations were observed for cancers of the stomach, colon and rectum, liver, breast and ovary. For all these diseases, significant increased risks were found also for ethanol intake of 25 g per day. No significant nor consistent relation was observed for cancers of the pancreas, lung, prostate or bladder. Allowance for tobacco appreciably modified the relations with laryngeal, lung and bladder cancers, but not those with oral, oesophageal or colorectal cancers. This meta-analysis showed no evidence of a threshold effect for most alcohol-related neoplasms. The inference is limited by absence of distinction between lifelong abstainers and former drinkers in several studies, and the possible selective inclusion of relevant sites only in cohort studies.
The relationship between breast cancer risk and family history of cancer in first-degree relatives was investigated using data from a multicentric case-control study conducted in Italy between June 1991 and April 1994 on 2,569 women aged less than 75 years, with histologically confirmed incident breast cancer, and 2,588 control women admitted to hospital for acute, non-neoplastic, non-gynaecological conditions. Relative to women with no history, those with a family history of breast cancer had an odds ratio (OR) of 2.4 [95% confidence interval (CI) 1.9-3.0], and those with family history of intestinal cancer had an OR of 1.3 (95% CI 1.0-1.7). No significant relations emerged between breast cancer risk and family history of prostate (OR 1.1), ovarian (OR 1.3), cervical or endometrial (OR 1.2) or other cancers, except gallbladder (OR 8.6). The OR for family history of any type of cancer except breast cancer was 1.1. For family history of breast cancer the ORs were similar across strata of age of the proband, being 2.4 below age 45, 2.2 at age 45-59 and 2.7 above age 60, and whether the relative affected was the mother, sister(s) or both, while the risk appeared higher if the age at onset of breast cancer in the relative was lower than 40 years (OR 3.5), rather than higher (OR 2.2). Thus, our results, based on the investigation of all neoplasms in first-degree relatives, confirm that breast cancer risk is increased in women with a family history of breast cancer, while there was no material association with family history of cancer in general, excluding breast cancer.
To estimate the mortality trends and spatial patterns for breast cancer in Córdoba (Argentina) in the period 1986-2006 taking into account age, calendar year, and birth cohort effects. Mortality data were provided by the Department of Statistics, Ministry of Health of Córdoba. Time trends in breast cancer mortality were analyzed using joinpoint analysis and age-period-cohort models. A random-intercept log-linear model was also used to assess the spatial pattern. Breast cancer age standardized mortality rates rose by 1.4% (95% confidence interval 0.2-2.6) per year from 1986 to 1997, and thereafter both breast and total cancer rates declined [-2.5% (-4 to -1.0) and -1.6% (-2.3 to -0.8), respectively]. In age-specific analysis the decline was mainly at age 20-49 years [-2.4% (-4 to -0.9)]. Rates over most recent calendar years decreased, mainly in the most urbanized districts. Age-period-cohort models for Córdoba province and Córdoba Capital showed a favorable cohort effect for generations born after 1955. A decreasing trend in breast cancer mortality was found in Córdoba, especially at younger ages and in most urbanized areas. This could be attributed to some unidentified favorable factors in generations born after 1955.
The possible relationship between fibre intake and breast cancer risk has been considered in several studies, but the issue is still unsettled. Epidemiological data are compatible with moderate protection from fibre-rich foods against the risk of breast cancer, but also with an absence of association. The apparently inconsistent results may be due to chance or bias, to different approaches to data analysis and interpretation, but may also reflect heterogeneity in the dietary sources of fibres (cereals or vegetables and fruit) in various populations, and different correlates of fibre intake.
Trends in death certification rates from pancreatic cancer over the period 1955-1989 were analyzed for 25 European countries (excluding the former Soviet Union and a few smaller countries). In 1985-1989, rates for males ranged between 5.3/100,000 (age-standardized world population) in Spain and 10.3/100,000 in Hungary and Czechoslovakia. Other high-mortality areas were located in Northern Europe (Finland, Iceland, Ireland, Denmark) and Central Europe (Austria, Poland, Germany), whilst mortality was lower in Southern Europe (Portugal, Greece). Between 1955 and 1989, mortality rates increased in all the countries considered, the change ranging between 6% in Scotland and 279% in Spain; the rises were higher in the Mediterranean and Eastern European countries than in Northern Europe. Among females, Nordic countries such as Iceland, Sweden and Denmark had the highest mortality rates in 1985-1989 (over 6/100,000) and, as for males, Southern Europe (Spain, Portugal, Greece) appeared as a low-mortality area (around 3/100,000). During the 1955-1989 period, upward trends were observed in all the countries studied, with the highest increase in Greece, Italy, Bulgaria, Poland and Spain. A negative correlation was observed between the percent change in mortality rates between 1955-1959 and 1985-1989 and the rate in 1955-1959 among both males (r = -0.95, p < 0.001) and females (r = -0.81, p < 0.001). Thus, a systematic levelling of rates was observed in most countries, with the exception of the UK and some Nordic countries, whose rates were already high in the late 1950s. Tobacco smoking and dietary factors could account for some of the generalized upward trends. Improved diagnostic and death certification of the disease might also partially explain the observed figures.
Several unfavourable trends and epidemics of fatal asthma have been registered in various developed countries of Europe, the United States and New Zealand over the last three decades. These have been related to problems in the treatment of the disease, following the introduction and/or inappropriate utilization of selected beta-agonist treatments. Thus, trends in mortality rates from bronchial asthma have been analyzed in Switzerland, where the Eighth Revision of the International Classification of Diseases has been in operation from 1969 to 1993. Overall age-standardized mortality rates (world standard) declined, from 4.3/100,000 males in 1969-73 to 2.8 in 1989-93, and from 2.0 to 1.5/100,000 females. The declines were consistent in both sexes for the age group 35 to 64 years, and some downward trend was observed also above age 65, particularly in males. Asthma mortality trends were inconsistent in children and young adults ( < 35 years), with some increase in males aged 15 to 34 after 1983, in the absence however of any significant linear trend in rates. Thus, trends in asthma mortality in Switzerland showed a moderate and steady decline in rates, particularly in middle aged males, in the absence of any systematic upward trend or epidemic peak. Still, the trends were only moderately favourable, and in the early 1990's about 250 deaths per year were attributed in Switzerland to bronchial asthma, i.e. an avoidable, in principle, cause of death.
Summary Surface expression of a functional B cell antigen receptor ( BCR ) is essential for the survival and proliferation of mature B cells. Most types of B‐cell lymphoproliferative disorders retain surface BCR expression, including B‐cell non‐Hodgkin lymphomas (B‐ NHL ) and chronic lymphocytic leukemia ( CLL ). Targeting BCR effectors in B‐ NHL cell lines in vitro has indicated that this signaling axis is crucial for malignant B cell growth. This has led to the development of inhibitors of BCR signaling, which are currently used for the treatment of CLL and several B‐ NHL subtypes. Recent studies based on conditional BCR inactivation in a MYC ‐driven mouse B‐cell lymphoma model have revisited the role of the BCR in MYC ‐expressing tumor B cells. Indeed, lymphoma cells losing BCR expression continue to grow unless subjected to competition with their BCR ‐expressing counterparts, which causes their elimination. Here, we discuss the molecular nature of the fitness signal delivered by the BCR to MYC ‐expressing malignant B cells, ensuring their preferential persistence within a rapidly expanding tumor population. We also review growing evidence of Ig‐negative cases belonging to several B‐ NHL subtypes and CLL , and discuss the clinical implications of these findings in relation to an emerging picture of clinical resistances to anti‐ BCR therapies.
a‘Mario Negri’ Institute for Pharmacological Research, Milano and bInstitute of Medical Statistics, University of Milan, Milano, Italy Sponsorship: This work was supported by the Italian Association for Research on Cancer, Italian League against Cancer and the Italian Ministry of Education (COFIN 2003).
