Public awareness of risk factors for cancer among the Japanese general population: A population-based survey

BACKGROUND: The present study aimed to provide information on awareness of the attributable fraction of cancer causes among the Japanese general population. METHODS: A nationwide representative sample of 2,000 Japanese aged 20 or older was asked about their perception and level of concern about various environmental and genetic risk factors in relation to cancer prevention, as a part of an Omnibus Survey. Interviews were conducted with 1,355 subjects (609 men and 746 women). RESULTS: Among 12 risk factor candidates, the attributable fraction of cancer-causing viral and bacterial infection was considered highest (51%), followed by that of tobacco smoking (43%), stress (39%), and endocrine-disrupting chemicals (37%). On the other hand, the attributable fractions of cancer by charred fish and meat (21%) and alcohol drinking (22%) were considered low compared with other risk factor candidates. For most risk factors, attributable fraction responses were higher in women than in men. As a whole, the subjects tended to respond with higher values than those estimated by epidemiologic evidence in the West. The attributable fraction of cancer speculated to be genetically determined was 32%, while 36% of cancer was considered preventable by improving lifestyle. CONCLUSION: Our results suggest that awareness of the attributable fraction of cancer causes in the Japanese general population tends to be dominated by cancer-causing infection, occupational exposure, air pollution and food additives rather than major lifestyle factors such as diet

ZFAT is an antiapoptotic molecule and critical for cell survival in MOLT-4 cells

AbstractZFAT (also known as ZNF406), originally identified as a candidate gene for autoimmune thyroid disease, encodes a zinc-finger protein, however, its function has not been elucidated. Here, we report that human ZFAT protein is expressed in peripheral B and T lymphocytes and a human acute T lymphoblastic leukaemia cell line, MOLT-4 cells. Intriguing is that mouse ZFAT expression in CD4+ lymphocytes is increased during blast formation. Furthermore, ZFAT-knockdown in MOLT-4 induces apoptosis via activation of caspases. These results suggested that ZFAT protein is a critical regulator involved in apoptosis and cell survival for immune-related cells

Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection

Allograft rejection is induced by graft tissue infiltration of alloreactive T cells that are activated mainly in secondary lymphoid organs of the host. DOCK2 plays a critical role in lymphocyte homing and immunological synapse formation by regulating the actin cytoskeleton, yet its role in the in vivo immune response remains unknown. We show here that DOCK2 deficiency enables long-term survival of cardiac allografts across a complete mismatch of the major histocompatibility complex molecules. In DOCK2-deficient mice, alloreactivity and allocytotoxicity were suppressed significantly even after in vivo priming with alloantigens, which resulted in reduced intragraft expression of effector molecules, such as interferon-γ, granzyme B, and perforin. This is mediated, at least in part, by preventing potentially alloreactive T cells from recruiting into secondary lymphoid organs. In addition, we found that DOCK2 is critical for CD28-mediated Rac activation and is required for the full activation of alloreactive T cells. Although DOCK2-deficient, alloreactive T cells were activated in vitro in the presence of exogenous interleukin-2, these T cells, when transferred adoptively, failed to infiltrate into the allografts that were transplanted into RAG1-deficient mice. Thus, DOCK2 deficiency attenuates allograft rejection by simultaneously suppressing multiple and key processes. We propose that DOCK2 could be a novel molecular target for controlling transplant rejection

DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis

Neutrophils are highly motile leukocytes, and they play important roles in the innate immune response to invading pathogens. Neutrophil chemotaxis requires Rac activation, yet the Rac activators functioning downstream of chemoattractant receptors remain to be determined. We show that DOCK2, which is a mammalian homologue of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, regulates motility and polarity during neutrophil chemotaxis. Although DOCK2-deficient neutrophils moved toward the chemoattractant source, they exhibited abnormal migratory behavior with a marked reduction in translocation speed. In DOCK2-deficient neutrophils, chemoattractant-induced activation of both Rac1 and Rac2 were severely impaired, resulting in the loss of polarized accumulation of F-actin and phosphatidylinositol 3,4,5-triphosphate (PIP3) at the leading edge. On the other hand, we found that DOCK2 associates with PIP3 and translocates to the leading edge of chemotaxing neutrophils in a phosphatidylinositol 3-kinase (PI3K)–dependent manner. These results indicate that during neutrophil chemotaxis DOCK2 regulates leading edge formation through PIP3-dependent membrane translocation and Rac activation

Association of body mass index and height with risk of prostate cancer among middle-aged Japanese men

In a population-based prospective study of 49 850 Japanese men, body mass index and height were not significantly associated with risk of prostate cancer (311 cases), although small positive effects could not be ruled out in advanced cases (91 cases)