Mother Nature's tightly held secrets to healthy aging are in danger of being wrested away. The genes we inherit, the lives we lead and the places we live all affect our chances to evade major diseases and to maintain health as we grow older.
To help sort out how variations in these contributing factors influence health risks, Kaiser Permanente's Division of Research is creating one of the world's largest genetic and environmental information resources for health research, called the Research Program on Genes, Environment, and Health (RPGEH).
"This is going to be the largest and most comprehensive database for doing genetic epidemiology research," says Neil Risch, PhD, head of the Institute for Human Genetics at UCSF and co-chair of the Department of Epidemiology. Risch is an adjunct investigator at the Kaiser Permanente Division of Research and co-director of the RPGEH.
In September 2009, the RPGEH and UCSF received $25 million in federal stimulus funds. The source was a new, two-year grant from the National Institutes of Health. The funds will enable Risch and colleagues to genotype DNA from 100,000 RPGEH participants. The genotyping project is a collaboration between the UCSF Institute for Human Genetics and the RPGEH.
As a result of this funding, in just a few years, scientists around the world will be able to tap into a new data resource, which will be the biggest of its kind to focus on genetic variation and environmental exposures in an older population. The average age of individuals whose genetic information will be genotyped for the project is 65.
More than 125,000 Kaiser members already have contributed saliva samples to the RPGEH for DNA genotyping.
UCSF Scientist Wins $89M Grant to Study Anal Cancer In HIV-Infected People
By Elizabeth Fernandez |UCSF.edu| November 22, 2013
Joel Palefsky, MD
A UC San Francisco investigator has won an eight-year grant from the National Cancer Institute for a major investigation into anal cancer, a debilitating and sometimes fatal disease largely concentrated among people with HIV.
The total amount of the award over the life of the grant is projected to be approximately $89 million.
Anal cancer disproportionately affects HIV-infected men and women, but the rate of infection is rising among people who do not have HIV and without active intervention, and the number of cases is expected to continue to grow in the general population.
Like cervical cancer and some oral cancers, most cases of anal cancer are associated with human papillomavirus (HPV). Vaccination has been shown to reduce the risk, but the majority of HIV-infected individuals currently at risk for anal cancer are older than age 26, do not qualify for vaccination, and may already have been exposed to the form of HPV known to cause anal cancer.
“Given these strong biological similarities, it is very possible that biomarkers and treatments identified in the study will be applicable to cervical and HPV-associated oral cancer as well,” said Joel Palefsky, MD, a UCSF professor of medicine and principal investigator of the anal cancer project.
The study will focus on determining the effectiveness of treating anal high-grade squamous intraepithelial lesions (HSIL), which are caused by chronic HPV infection, in reducing the incidence of anal cancer in HIV-infected men and women.
Combined with the possibility that anal cancer is preventable, the incidence of anal cancer is unacceptably high and calls for urgent intervention, Palefsky said.
“Compared with the general population, the incidence of anal cancer is increased more than 100-fold among some risk groups of HIV-infected persons, including many who are successfully treated with combination antiretroviral therapy,” Palefsky said. “There is evidence that anal HSIL is the precursor to invasive anal cancer, which makes it a great target for prevention.”
In a major scientific review of research on e-cigarettes, UC San Francisco scientists found that industry claims about the devices are unsupported by the evidence to date, including claims that e-cigarettes help smokers quit.
The review marks the first comprehensive assessment of peer-reviewed published research into the relatively new phenomenon of electronic cigarettes.
The devices, which are rapidly gaining a foothold in popular culture particularly among youth, are marketed as a healthier alternative to tobacco smoking, as an effective tool to stop smoking, and as a way to circumvent smoke-free laws by allowing users to "smoke anywhere." Often the ads stress that e-cigarettes produce only "harmless water vapor."
But in their analysis of the marketing, health and behavioral effects of the products, which are unregulated, the UCSF scientists found that e-cigarette use is associated with significantly lower odds of quitting cigarettes. They also found that while the data are still limited, e-cigarette emissions "are not merely 'harmless water vapor,' as is frequently claimed, and can be a source of indoor air pollution.
The long-term biological effects of use are still unknown, the authors said.
Stanton Glantz, PhD
Neil Benowitz, MD
Rachel Grana, PhD, MPH
In tackling the question of whether e-cigarette use is helping or harming the nation's tobacco control efforts, the authors analyzed 84 research studies on e-cigarettes and other related scientific materials.
They concluded that e-cigarettes should be prohibited wherever tobacco cigarettes are prohibited and should be subject to the same marketing restrictions as conventional cigarettes.
The paper is published May 12, 2014 in the American Heart Association's journal Circulation.
E-cigarettes deliver a nicotine-containing aerosol popularly called "vapor" to users by heating a solution commonly consisting of glycerin, nicotine and flavoring agents. E-liquids are flavored, including tobacco, menthol, coffee, candy, fruit and alcohol flavorings.
Despite many unanswered questions about e-cigarette safety, the impact on public health, and whether the products are effective at reducing tobacco smoking, e-cigarettes have swiftly penetrated the marketplace in the United States and abroad in both awareness and use. Sold by the major multinational tobacco and other companies, the devices are aggressively marketed in print, television and the Internet with messages similar to cigarette marketing in the 1950s and 1960s, even in the U.S. and other countries that have long banned advertising for cigarettes and other tobacco products.
In one indication of the swiftness by which the devices have been embraced, in the U.S. youth "ever use" of the devices rose from 3.3 percent in 2011 to 6.8 percent the following year; in Korea, youth "ever use" of e-cigarettes rose from .5 percent in 2008 to 9.4 percent in 2011. "Ever use" means whether one has smoked the product even just once.
Furthermore, most adults and youths who use e-cigarettes are engaging in "dual use" – smoking both e-cigarettes and conventional cigarettes.
While most youth using e-cigarettes are dual users, up to a third of adolescent e-cigarette users have never smoked a conventional cigarette, indicating that some youth are starting use of the addictive drug nicotine with e-cigarettes.
The report also tackles secondhand exposure.
"E-cigarettes do not burn or smolder the way conventional cigarettes do, so they do not emit side-stream smoke; however, bystanders are exposed to aerosol exhaled by the user," said the authors. Toxins and nicotine have been measured in that aerosol, such as formaldehyde, acetaldehyde, acetic acid and other toxins emitted into the air, though at lower levels compared to conventional cigarette emissions.
At UCSF, Esserman has worked in the clinic, in research, and with interdisciplinary teams of clinicians and researchers. The result of her work has been a cross-disciplinary approach to battling breast cancer, including the best care for patients and the best platform to integrate translational research into breast cancer care.
Esserman is a leader of the innovative I-SPY TRIAL model, designed to accelerate the identification and approval of effective new agents for women with high risk breast cancers. The goal of the I-SPY TRIAL model is to shave several years and tens to hundreds of millions of dollars off the drug development process. The trial paradigm is now being developed for use in other disease domains.
In 2009, Esserman led the creation of the University of California-wide Athena Breast Health Network, a learning system designed to integrate clinical care and research as it follows 150,000 women from screening through treatment and outcomes.
In March 2015, she received one of the first five major grants funded through the Patient-Centered Outcomes Research Institute’s (PCORI) Pragmatic Clinical Trials initiative. The $14 million grant funds the WISDOM study to learn how to improve breast cancer screening by testing and comparing the safety and efficacy of a personalized screening strategy informed by each woman’s breast cancer risk and preferences against the standard of annual screening. The WISDOM Study is slated to open in late summer 2016.
Internationally Recognized Thought Leader
The findings from her research have been published in 250 articles in peer-reviewed journals covering all aspects of breast health on topics that include information systems, immunology, decision-making, health policy and the use of imaging.