Research Highlights Cancer Epidemiology Program
- Alice Whittemore, PhD, professor of epidemiology and biostatistics has received the Saul Rosenberg Research Award from the Northern California Cancer Center.
- Dee West, Ph.D. Professor, and Bang Nguyen, Dr.PH , Consulting Assistant Professor, have received a 2009 CTSA Seed Grant Award for Building Community Academic Partnerships for Cancer Control Research
- Russ Altman and Phil Lavori have been appointed to the Medical School’s Genotyping Task Force to review the broad and important questions concerning introducing students to personal genotyping. Activities of this task force involve developing a 2009-2010 Proposal for Introducing Students to Genotyping.
- Because an effective amount of warfarin can vary by as much as 10-fold among individuals, physicians currently start most of their patients on a low dose and ramp up gradually until blood tests indicate the dose is correct — a process that can take months. Russ Altman, a Cancer Epidemiology Program member who chairs Stanford's bioengineering department, and Teri Klein, PhD, a senior research scientist in genetics at the School of Medicine, solicited, in collaboration with others, warfarin dose-response information from over 21 sites — known as the International Warfarin Pharmacogenetics Consortium — in nine countries for inclusion in the study, which was published in the Feb. 19 issue of the New England Journal of Medicine. Although this study is not the first to show the advantage of incorporating genetic information into prescribing patterns, it is by far the largest and most inclusive: It includes information on more than 5,000 patients from many ethnic groups. Members of the consortium are currently working to design a clinical trial to confirm the results of this prospective study.
- The Stanford School of Medicine received a Clinical and Translational Science Award, linking Stanford to the CTSA consortium of 38 academic health centers working to speed medical progress, each according to its own strategy. Stanford’s approach will focus on interdisciplinary connections between the medical school, the rest of the campus and innovators in business based in Silicon Valley. The crux of the effort will be the Stanford Center for Clinical and Translational Education and Research, an independent institute that will operate outside traditional school boundaries. The program’s co-directors are Philip Lavori, PhD, professor of biostatistics and chair of health research and policy and a member of the Cancer Epidemiology Program; Charles Prober, MD, professor of pediatrics and senior associate dean for medical student education; Branimir Sikic, MD, professor of oncology; and David Stevenson, MD, professor of pediatrics and senior associate dean of academic affairs.
- To determine who should be tested for BRCA1 and BRCA2 mutations, genetic counselors frequently use computer models that assess specific variables for each woman, such as the number of relatives affected by breast and ovarian cancer, the age of each relative at onset of the condition and how closely the woman is related to her affected relatives.Allison Kurian and her colleagues used two widely accepted computer models, named BRCAPRO and Myriad II, to predict the presence of the mutations in 200 white women and 200 Asian-American women at cancer genetics clinics in four locations. They sequenced the BRCA1 and BRCA2 genes of all of the study subjects and compared them to the models’ predictions. The researchers found that the models were highly accurate in predicting the presence of mutations in white women; one program identified 24 of the 25 women with BRCA1 or BRCA2 mutations and the other identified all 25. However, both programs performed much worse in predicting the 49 Asian women in the study sample with mutations. One program predicted that only 25 of the 49 women would carry mutations, while the other recommended testing of 26 women. Kurian's study results point out the need for further investigation into the genetic variability of different ethnic groups. In addition to previously identified, clinically important mutations of the genes, the researchers identified more “variants of unknown significance” in the BRCA1 and BRCA2 genes of Asian women than in white women.
- A three-year, career development award will fund Allison Kurian’s study, “Optimizing the Use of Breast Cancer Risk Reduction Strategies by Patients and Physicians.” The study builds on research by Kurian and Sylvia Plevritis, PhD, associate professor of radiology, which was funded by a 2007 Stanford Cancer Center Developmental Seed Award. The goal of the project is to develop a tool to help women at increased risk for breast cancer make more informed choices about how best to manage that risk. Dr. Sylvia Plevritis will act as mentor on the new research project.
- Dean Felsher, MD, PhD, associate professor of oncology and of pathology and Sylvia Plevritis, PhD, associate professor of radiology, are senior researchers on a study identifying a precise threshold level of the signaling molecule Myc that determined the fate of tumor cells in a cancer of the immune system in mice. Above the threshold, high levels of Myc drove immune cells to grow too large and multiply uncontrollably. When the researchers lowered Myc levels below the threshold, the same cells shrank to normal size, stopped multiplying and began dying normally.
- Dr Esther John is the lead author of a work, published in the Dec. 26 issue of the Journal of the American Medical Association, marking the largest study to date to look at the prevalence of BRCA1 mutations among patients in the four ethnic and racial groups. A genetic mutation already known to be more common in Ashkenazi Jewish breast cancer patients is also prevalent in Hispanic and young African-American women with breast cancer, according to one of the largest, multiracial studies of the mutation to date. News release .
- Dr Ronald Davis has received funding for a project entitled "Development of Selectors for Cancer Mutation Analysis" through a Cancer Genome Atlas award. This project will develop methods for high-throughput isolation of genomic regions for DNA sequence analysis.
- A baseline snapshot of working conditions and health concerns of nail salon workers in the first step of studies to determine the health impact of their exposure to potential carcinogens in nail care products: The baseline survey, conducted by researchers at the Northern California Cancer Center, the School of Medicine and the Stanford Cancer Center, was the beginning of a larger effort to learn whether the women have a higher risk of breast cancer and other diseases, as has been suggested by some smaller studies. News Release
- Researchers find Genetic Risk Factors for Prostate Cancer: Multiple research findings showing a link between genetic variants on chromosome 8 and prostate cancer risk. From NCI Genetics and Epidemiology Research Highlights: "These findings build on an association found last year between a variant at 8q24 (rs1447295) and prostate cancer risk. First, the Iceland-based company, deCODE Genetics, demonstrated that individuals with specific polymorphisms at rs14472975 and rs16901979 accounted for about 11% to 13% of prostate cancer cases in individuals of European decent and 31% of cases in African Americans. Second, the Cancer Genetics Markers of Susceptibility (CGEMS) initiative validated the original deCODE Genetics finding (rs1447295) and found a third locus at 8q24 (rs6983267) that strongly predicts prostate cancer risk. Independently, this locus may be responsible for up to 20 percent of prostate cancer cases among white men in the United States. Third, the EGRP-sponsored Multiethnic Cohort Study identified seven genetic variants that independently predict risk for prostate cancer in the locus at 8q24. Most of the seven variants were of highest frequency in African Americans. The high prevalence of these deleterious variants may contribute to the higher rate of prostate cancer among African Americans. The Breast and Prostate Cancer Cohort Consortium (BPC3) also confirmed deCODE Genetics findings that variation at rs1447295 is strongly associated with prostate cancer risk. However, they found no association between rs1447295 and breast cancer risk. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet. 2007 Apr 1; [Epub ahead of print] Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, Neubauer J, Tandon A, Schirmer C, McDonald GJ, Greenway SC, Stram DO, Le Marchand L, Kolonel LN, Frasco M, Wong D, Pooler LC, Ardlie K, Oakley-Girvan I, Whittemore AS, Cooney KA, John EM, Ingles SA, Altshuler D, Henderson BE, Reich D. Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet. 2007 Apr 1.
- Helicobacter pylori infection associated with reduced risk of esophageal adenocarcinoma. An increase in the incidence of esophageal adenocarcinoma has coincided with a decrease in the prevalence of Helicobacter pylori infection. Whether these two phenomena are associated is unknown. Dr. Julie Parsonnet and colleagues conducted a nested case-control study of 128,992 members of an integrated health care system who had participated in a multiphasic health checkup (MHC) during 1964-1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Three control subjects from the MHC cohort were matched to each case. The authors found that subjects with H. pylori infections were less likely than uninfected subjects to develop esophageal adenocarcinoma. This association was restricted to case subjects and control subjects <50 years old at the MHC. In patients with H. pylori infections, the odds-ratio for those who tested positive for IgG antibodies to the CagA protein was similar to that for those who tested negative for it. Body mass index and cigarette smoking were strong independent risk factors for development of esophageal adenocarcinoma (de Martel C et al, J Infect Dis. 2005 Mar 1;191(5):761-7).
- Unknown genetic factors influence breast and ovarian cancer risks in both carriers and noncarriers of BRCA mutations. Dr Alice Whittemore, Dr Esther John, Dr Valerie McGuire, Dr Dee West and colleagues evaluated breast and ovarian cancer incidence in relatives of patients with cancers of the breast or ovary who were recruited from the Northern California SEER registry, and who were tested for mutations of BRCA1 and BRCA2. The authors found that, relative to the general population, ovarian cancer risk was higher than breast cancer risk in families of ovarian cancer patients. Conversely, breast cancer risk was higher than ovarian cancer risk in families of breast cancer patients. This site-specificity was seen both in families that did and did not segregate BRCA mutations. These patterns support the presence of genes that modify risk specific to cancer site, in both carriers and noncarriers of BRCA1 and BRCA2 mutations (Lee et al Cancer Epid Biomarkers and Prev. 2006 Feb;15(2):359-63).
- 2300 breast cancer cases in California may be avoided through population change in the characteristics, hormone replacement therapy (HRT), alcohol consumption, and breast feeding. Dr Sally Glaser and Dr Christina Clarke have estimated the number of breast cancers in the US that might be prevented if women changed their behaviors with respect to three risk factors: alcohol consumption, HRT use, and lack of breastfeeding. Using the prevalence of these risks and the attributable risk of each, they determined that each year in California over 500 breast cancer cases are due to HRT use, over 1000 cases are due to consuming two or more alcoholic drinks per day, and 800 cases could be prevented if women who did not breast feed changed this behavior (BMC Cancer. 2006 Jun 27;6:170.)
- A study of patient’s perception of cancer care confirms wide disparities by race and other factors. Dr West and colleagues surveyed a population-based cohort of 1.067 colorectal cancer patients in within one month of diagnosis, to inquire regarding perceived problems in six cancer care domains. Compared to white patients, African American, Hispanic, and Asian patients reported more problems with coordination of care, access to care, and health information. In addition, African Americans reported more problems with psychosocial care and more Hispanics expressed problems with receiving treatment information. As expected, non-English speaking patients had more problems in all six domains, with non-English speaking Hispanic patients especially lacking confidence in providers. Many difference were also seen by education, income, and age, but no differences were seen by gender or marital status (Ayanian J, et. al., J Clin Oncol:23:1-11, 2005).
This document was last modified: Thursday, 12-Nov-2009 22:17:04 PST
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