Incidence of Invasive Cancers Following Squamous Cell Skin Cancer

The authors describe the incidence of new primary cancers among 4,639 cases of squamous cell skin cancer (SCC) diagnosed between 1974 and 1994 in the cancer registries of the Swiss cantons of Vaud and Neuchâtel (total person-years at risk = 23,152). Overall, 729 metachronous cancers were observed versus 527.6 expected, corresponding to a standardized incidence ratio (SIR) of 1.4 (95% confidence interval (Cl) 1.3-1.5). After exclusion of skin cancers, however, 384 second primary neoplasms were observed versus 397.2 expected (SIR = 1.0). Excesses were observed for cancers of the lip (SIR = 3.1) and lung (SIR = 1.3), for basal cell (SIR = 4.3) and melanomatous skin cancers (SIR = 3.3), and non-Hodgkin's lymphomas (SIR = 1.7). Rates were elevated for cancers of the salivary glands (SIR = 4.3) and for Hodgkin's disease (SIR = 2.7), and, below age 65 years, for cancers of the lung (SIR = 1.6), breast (SIR = 1.5), and prostate (SIR % 1.8), for Hodgkin's disease (SIR = 15.8), as well as for all neoplasms except skin (SIR = 1.2; 95% Cl 1.0-1.5). The cumulative risk of basal cell skin cancer reached 17% after 15 years. The authors believe that the excesses for basal cell carcinomas and melanomas of the skin following SCC, and possibly of lymphomas, were likely attributable to common phenotypic characteristics and exposure to UV radiation. The elevated rates of lung cancer are suggestive for a role of tobacco as a cause of squamous cell skin cance

Incidence of Invasive Cancers following Basal Cell Skin Cancer

To obtain quantitative information on the risk of invasive cancers following a diagnosis of basal cell carcinoma (BCC) of the skin, patients with incident BCC cases listed in the cancer registries of the Swiss cantons of Vaud and Neuchatel between 1974 and 1994 were actively followed up through December 31, 1994, for the occurrence of subsequent invasive neoplasms. Among 11,878 persons with incident BCC who were followed for a total of 76,510 person-years at risk, 1,543 metachronous cancers were observed versus 1,397.9 expected, corresponding to a standardized incidence ratio (SIR) of 1.1 (95% confidence interval (Cl) 1.0-1.2). However, after exclusion of skin cancers (mostly squamous cell carcinoma and melanoma), 975 second primary cancers were observed versus 1,059 expected (SIR = 0.9, 95% Cl 0.8-1.0). Significant excesses were registered for cancer of the lip (SIR = 2.2), for squamous cell skin cancer (SIR = 4.5) and melanoma of the skin (SIR = 2.5), and for non-Hodgkin's lymphoma (SIR = 1.9). The SIRs were also above unity, though not significantly, for cancers of the salivary glands (SIR = 2.8) and the small intestine (SIR = 2.1) and for soft-tissue sarcomas (SIR = 1.7). The SIR for lung cancer was 0.9. The SIRs for salivary gland and skin cancer were appreciably greater below age 70 years. For most sites, particularly for squamous cell cancer and melanoma of the skin, the SIRs remained elevated 5 or more years after BCC diagnosis. The cumulative incidence of squamous cell skin cancer was 13% at 19 years; this stresses the importance of carefully monitoring skin lesions among persons previously diagnosed with BCC. Am J Epidemiol 1998;147:722-

Model-Independent Searches for New Quarks at the LHC

New vector-like quarks can have sizable couplings to first generation quarks without conflicting with current experimental constraints. The coupling with valence quarks and unique kinematics make single production the optimal discovery process. We perform a model-independent analysis of the discovery reach at the Large Hadron Collider for new vector-like quarks considering single production and subsequent decays via electroweak interactions. An early LHC run with 7 TeV center of mass energy and 1 fb-1 of integrated luminosity can probe heavy quark masses up to 1 TeV and can be competitive with the Tevatron reach of 10 fb-1. The LHC with 14 TeV center of mass energy and 100 fb-1 of integrated luminosity can probe heavy quark masses up to 3.7 TeV for order one couplings.Comment: 37 pages, 11 figures, 7 table

Reconstructing Native American Population History

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved1–5. One contentious issue is whether the settlement occurred via a single6–8 or multiple streams of migration from Siberia9–15. The pattern of dispersals within the Americas is also poorly understood. To address these questions at higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. We show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call “First American”. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan-speakers on both sides of the Panama Isthmus, who have ancestry from both North and South America

Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found that breast tumorigenesis is accompanied by collagen crosslinking, ECM stiffening, and increased focal adhesions. Induction of collagen crosslinking stiffened the ECM, promoted focal adhesions, enhanced PI3 kinase (PI3K) activity, and induced the invasion of an oncogene-initiated epithelium. Inhibition of integrin signaling repressed the invasion of a premalignant epithelium into a stiffened, crosslinked ECM and forced integrin clustering promoted focal adhesions, enhanced PI3K signaling, and induced the invasion of a premalignant epithelium. Consistently, reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence. These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy. © 2009 Elsevier Inc. All rights reserved