Publications

Response: Re: False-Positive Results in Cancer Epidemiology: A Plea for Epistemological Modesty

We thank Drs Cogliano and Straif for their interest in our Commentary calling for increased epistemic humility in the interpretation of new epidemiological findings on possible occupational and environmental causes of cancer. We made reference in our Commentary to two International Agency for Research on Cancer (IARC) monographs ( 1 , 2 ), not as criticisms of the monographs themselves but rather as examples of attempts to reach a consensus

Faculty Opinions recommendation of Attenuation of HIV-associated human B cell exhaustion by siRNA downregulation of inhibitory receptors.

Chronic immune activation in HIV-infected individuals leads to accumulation of exhausted tissue-like memory B cells. Exhausted lymphocytes display increased expression of multiple inhibitory receptors, which may contribute to the inefficiency of HIV-specific antibody responses. Here, we show that downregulation of B cell inhibitory receptors in primary human B cells led to increased tissue-like memory B cell proliferation and responsiveness against HIV. In human B cells, siRNA knockdown of 9 known and putative B cell inhibitory receptors led to enhanced B cell receptor-mediated (BCR-mediated) proliferation of tissue-like memory but not other B cell subpopulations. The strongest effects were observed with the putative inhibitory receptors Fc receptor-like-4 (FCRL4) and sialic acid-binding Ig-like lectin 6 (Siglec-6). Inhibitory receptor downregulation also led to increased levels of HIV-specific antibody-secreting cells and B cell-associated chemokines and cytokines. The absence of known ligands for FCRL4 and Siglec-6 suggests these receptors may regulate BCR signaling through their own constitutive or tonic signaling. Furthermore, the extent of FCLR4 knockdown effects on BCR-mediated proliferation varied depending on the costimulatory ligand, suggesting that inhibitory receptors may engage specific pathways in inhibiting B cell proliferation. These findings on HIV-associated B cell exhaustion define potential targets for reversing the deleterious effect of inhibitory receptors on immune responses against persistent viral infections. PMID: 21633172 Funding information This work was supported by: Intramural NIH HHS, United States Howard Hughes Medical Institute, United States

Some Further Consideration on the Role of Oral Contraceptives in Breast Carcinogenesis

Available evidence concerning oral contraceptives and their potential interaction with reproductive history on breast cancer risk is reviewed. The relative risks in 15 out of 15 studies were above unity among younger women (i.e., below age 35 and perhaps up to 45) for long-term oral contraceptive use, although apparent heterogeneities emerged in the risk estimates. The overall evidence is reassuring in subsequent age groups, whereas the modifying effects or interactions between oral contraceptives, reproductive factors and breast cancer risk are still largely undefined. Thus we suggest that, besides chance and bias, the apparent discrepancies between various studies should be considered within the framework of the complex time- and age-effects of hormone-related risk factors on breast carcinogenesis.

Cancer epidemiology and public health

Abstract Neoplasms continue to dominate globally as one of the major sources of human disease and death. From a biological, clinical, and public health point of view, it is important to differentiate between a malignant and benign neoplasm. There are multiple causes of cancer and understanding the attributable risk factors for each cancer is important. This chapter covers the role of cellular and molecular mechanisms as well as the experimental and epidemiological approaches as determinants of select, common cancers. Promising approaches focused on prevention of the known causes, reducing its consequences, and notably in resource-constrained settings are highlighted.

Fruit and vegetable consumption and cancer risk in a Mediterranean population

Lung carcinoma trends by histologic type in Vaud and Neuch�tel, Switzerland, 1974-1994

Although changes in diagnostic practices may have played a role, the incidence data presented in this study suggest that adenocarcinoma is sustaining a new lung carcinoma epidemic, chiefly attributable to the switch to low-tar, filtered cigarettes. Its pattern seems remarkably similar in the two genders. Thus, the authors conclude that similar exposure to tobacco-related carcinogens leads to similar rates of histologic type-specific lung carcinoma incidence in males and females.

Cigar Smoking and Cancers of the Upper Digestive Tract

Pipe smoking has been related to the risk of cancers of the upper digestive and respiratory tract, but quantification of the risk for exclusive pipe smokers is still limited. To analyse the association between exclusive pipe smoking and cancers of the upper digestive tract, we used data from a series of case–control studies conducted in Italy and Switzerland between 1984 and 1999. After excluding cigarette and cigar smokers, 41 male oral and pharyngeal cancer cases, 52 male oesophageal cancer cases and 1,032 male controls were included in the present analysis. Odds ratios (OR) of cancers were estimated by the mean of unconditional multivariate logistic regression, including terms for age, study centre, education, body mass index, and alcohol drinking. Compared to never smokers, exclusive pipe smokers had an OR of 8.7 [95% confidence intervals (CI): 4.0–18.9] of all upper digestive tract cancers. The OR was 12.6 for oral and pharyngeal and 7.2 for oesophageal cancer. Pipe smokers who were also heavy alcohol drinkers had an OR of 38.8 (95% CI: 13.6–110.9) as compared to never smokers and light drinkers. Thus, pipe smoking and heavy alcohol drinking appears to interact at least on a multiplicative model. ' 2007 Wiley-Liss, Inc.

Smokeless tobacco use in Sweden and other 17 European countries

Excluding Sweden, current oral tobacco use was not commonly reported in the European countries surveyed and was similarly rare both in men and in women. In Sweden, however, use of smokeless tobacco was about 10-fold higher than the rest of Europe and more prevalent in men than in women.

Combined estrogen-progestogen menopausal therapy

Trends in mortality from motor vehicle accidents in Italy, 1955-79.

Trends in death certification rates from all motor vehicle accidents and motor-cycle accidents in Italy over the period 1955-79 were analysed. For both sexes, age-standardised mortality rates per 100,000 population increased steadily up to the early 1970's, reaching 40.08/100,000 males in 1972 and 11.05/100,000 females in 1973. Marked downward trends followed, and the 1977-79 rates were comparable with 1955 for males (around 28/100,000), though the total number of motor vehicles increased almost six-fold (and the number of cars over 14-fold). When age-specific rates were considered, the largest increases between the late 1950's and the early 1970's were for younger (under 25) and older (55 and over) males and younger (under 35) females. The decreases from 1974 onwards applied to both sexes and all age groups. Motor-cycle death rates increased in males up to the mid 1960's, mostly in younger (15-25) and older (over 55) age groups. A sudden, marked inversion of trends followed, starting from the younger age groups and spreading to all age groups in the mid 1970's. This pattern corresponds roughly to a 50% decrease in male death certification rates per registered motor-cycle. In absolute terms, the decline in the second half of the 1970's corresponds to about 4,000 fewer deaths per year. This is one of the major changes observed in mortality from any cause during the 1970's in Italy. Provisional data for the period 1980-82 suggest that further downward trends, albeit moderate, have continued.

Patterns of childhood cancer incidence and mortality in Europe

Oral contraceptives and benign breast disease: A case-control study

Serum liver enzymes and diabetes from the Rafsanjan cohort study

Elevated levels of ALT, AST, GGT and ALP are related to a higher odds of diabetes. Also, increased levels of ALT, GGT and ALP even within normal range were independently related with the increased odds of diabetes. These results indicated the potential of elevated liver enzymes as biomarkers for the possible presence of diabetes.

Olive Oil and Cancer Risk: an Update of Epidemiological Findings through 2010

Consumption of olive oil has been related to reduced risk of several diseases, including various neoplasms. In this paper, we reviewed epidemiological studies on olive oil and cancer published up to 2010. We performed a systematic literature search in the Medline database and, after assessment of relevant papers, we included 25 studies providing original data on olive oil consumption and cancer risk. We also performed a meta-analysis of studies of breast cancer, calculating the pooled relative risk (RR), and the corresponding 95% confidence intervals (CI), for high vs. low olive oil consumption. Several studies conducted in Southern Europe reported olive oil consumption as a favourable indicator of breast, digestive tract, and particularly upper aero-digestive tract cancers. For the latter, after adjustment for alcohol and tobacco use, the RRs between extreme levels of olive oil consumption were 0.3-0.4, and there was an over 5-fold difference in risk between subjects consuming mainly olive oil and those consuming mainly butter. The summary RR of breast cancer was 0.62 (95% CI, 0.44-0.88) for the highest vs. lowest level of olive oil consumption. Thus, preferring olive oil to other added lipids, particularly those rich in saturated fats, can decrease the risk of upper digestive and respiratory tract neoplasms, breast and, possibly, colorectal and other cancer sites.

IRF-4/MUM-1 Expression Is a Critical Switch in the Generation of Plasma Cells Versus Memory B-Cells.

High constant incidence of second primary colorectal cancer

Patients who had a colorectal cancer have a 1.5- to 2-fold excess risk of a second colorectal cancer as compared to the general population, the excess being higher at younger age at diagnosis. To further investigate the risk and the age-relation of the incidence of second primary colorectal cancer, we considered 9,389 first colon and rectal cancers registered in the Vaud Cancer Registry, Switzerland, between 1974 and 2008, and followed-up to the end of 2008 for a total of 44,113 person-years. There were 136 second colorectal cancers versus 90.5 expected, corresponding to a standardized incidence ratio (SIR) of 1.5 (95% confidence interval, CI, 1.3-1.8). The SIRs were not heterogeneous between men and women, and in strata of calendar year at diagnosis, duration of follow-up, and subsite. However, the SIR was 7.5 (95% CI 4.2-12.4) for subjects diagnosed below age 50 and declined thereafter to reach 1.0 (95% CI 0.6-1.6) at age 80 or over. Consequently, the incidence of second primary colorectal cancer was stable, and exceedingly high, around 300-400/100,000 between age 30-39 and 70 or over. This age pattern is consistent with the existence of a single mutational event in a population of highly susceptible individuals.

Dietary fibres and ovarian cancer risk

Perceived risk of cancer in Italy

Vecchia, C La1,2; Anelli, M3; Zuccato, E1; Fanelli, R1; Fioretti, F1; Sermeus, G4; Valdicelli, L4; Milazzo, N3 Author Information