Research Highlights from EGRP Grantees - 2011

Extramural investigators supported by the Epidemiology and Genomics Research Program (EGRP) were invited to nominate manuscripts published in 2011 based on their scientific merit, innovation, and/or potential public health impact. EGRP Program staff made the final selections based on scientific merit, innovation, and/or potential public health impact.

EGRP funds research in human populations to understand determinants of cancer occurrence and outcomes. EGRP is the largest funder of cancer epidemiology grants nationally and worldwide, supporting more than 400 grants and cooperative agreements annually. View a full list of active EGRP grants.External Web Site Policy

The research featured below was funded in full or in part by EGRP:

Body Mass Index

Breast Cancer

Colorectal Cancer

Family History


HPV Infection


Prostate Cancer


Association Between Body-Mass Index and Risk of Death Analyzed in 1 Million Asians

Obesity is associated with multiple chronic diseases, including several cancers. However, body mass index (BMI), which is often used to define underweight (BMI<18.5), overweight (BMI ≥ 25) and obesity (BMI ≥ 30), is based on studies primarily involving populations of European ancestry. The validity of BMI and its relationship with overall risk of death among Asians, who account for more than 60% of the world population, remains unclear. Based on the results of this pooled analysis of nearly one million East Asians, elevated risk of death was associated with both underweight and overweight, a U-shape association similar to that observed previously in studies conducted in populations of European descent. In Indians and Bangladeshis, however, a substantially elevated risk of death was associated with underweight. This study concludes that underweight remains a significant public health problem in many parts of Asia while the adverse effect of overweight starts to emerge.

Photo of the Asia Cohort Consortium 2010 Conference Presenters and attendees.

Zheng W, McLerran DF, Rolland B, et al. Association between body-mass index and risk of death in more than 1 million AsiansExternal Web Site Policy. N Engl J Med. Feb 2011;364(8):719-29.

This research is based on data from the Asia Cohort Consortium, which is supported in part by EGRP. Multiple EGRP-funded investigators participated in this consortium.

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Breast Cancer Risk Clarified for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations

A woman's lifetime risk of developing breast and/or ovarian cancer is greatly increased if she inherits a harmful mutation in BRCA1 or BRCA2. Such a woman has an increased risk of developing breast and/or ovarian cancer before menopause and often has multiple, close family members who have been diagnosed with these diseases. The likelihood that a breast and/or ovarian cancer is associated with a harmful mutation in BRCA1 or BRCA2 is highest in families with a history of multiple cases of breast cancer, cases of both breast and ovarian cancer, and who have one or more family members with two primary cancers.

Breast and Colon
Cancer Family Registries

This study did not find evidence of an increase in breast cancer risk for noncarriers of a family-specific BRCA1 or BRCA2 mutation. These results support the standard clinical practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to family-specific mutation. In the absence of any other strong risk factors, noncarriers should follow general population guidelines for breast cancer screening.

Kurian AW, Gong GD, John EM, et al. Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: findings from the Breast Cancer Family RegistryExternal Web Site Policy. J Clin Oncology. 2011 Dec 1;29(34):4505-9.

This research was funded in part by EGRP grants to Esther John, Ph.D., M.S.P.H., of the Cancer Prevention Institute of California; and Alice Whittemore, Ph.D., of Stanford University. These findings are based on data from the Breast Cancer Family Registry, which was supported by EGRP grants from 1995-2011.

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Common Genetic Variant Associated with Estrogen Receptor-Negative Breast Cancer

Women of African ancestry are more likely to be diagnosed with estrogen receptor (ER)-negative or triple-negative breast cancer (TNBC) than women of European ancestry. In addition, ER-negative breast cancers and TNBC are also predominantly prevalent in women with germline mutations in BRCA1. The last decade has seen advances in the treatment of ER-positive and human epidermal growth factor receptor 2/ErbB-2 (HER2)-positive breast cancers. However, outcomes for women with estrogen receptor (ER)-negative or TNBC remain poor. In addition, a better understanding of the common or shared biology of BRCA1-associated breast cancers and sporadic TNBC is needed.

This study identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690). The telomerase reverse transcriptase (TERT) and the cleft lip palate transmembrane protein 1-like (CLPTM1L) genes have been identified in other studies as potential cancer susceptibility genes. TERT encodes a telomerase protein, which is crucial for the maintenance of telomere length and chromosome stability. Additionally, several common variants in the TERT locus have been associated with several cancers, including breast cancer. On further analysis, the association with rs10069690 may be limited to TNBC, and not all HER2-negative tumors.

David Hunter

Fergus Couch

Haiman CA, Chen GK, Vachon CM, et al. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancerExternal Web Site Policy. Nat Genet. 2011 Oct 30;43(12):1210-4.

This research was funded in part by EGRP grants to Fergus Couch, Ph.D., of the Mayo Clinic; and David Hunter, M.B.B.S, Sc.D., of Harvard University.

Two of the consortia that contributed data to this study, the African-American Breast Cancer Consortium and the Breast and Prostate Cancer Cohort Consortium, also receive EGRP support.

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Cumulative Probability Estimated for False-Positives or Biopsy Recommendation After 10 Years of Screening Mammography

Results from randomized clinical trials and other studies show that screening mammography can help reduce the number of deaths from breast cancer among women ages 40 to 74, especially for those women more than age 50. This study estimated the cumulative probability of false-positive result and biopsy recommendations using ten years of annual or biennial screening data from the Breast Cancer Surveillance Consortium. Cumulative probability estimates suggest that after ten years of annual screening, more than half of women will receive at least one false-positive result, and 7-9% will receive a false-positive biopsy recommendation. Whereas biennial screening reduces false-positive results, it may be associated with a small increase in the proportion diagnosed with late-stage cancer.

Rebecca Hubbard

Hubbard RA, Kerlikowske K, Flowers CI, et al. Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort studyExternal Web Site Policy. Ann Intern Med. 2011 Oct 18;155(8):481-92.

This research was supported in part by an EGRP grant to Rebecca Hubbard, Ph.D., of the Group Health Research Institute. The Breast Cancer Surveillance ConsortiumExternal Web Site Policy (BCSC) is a research resource for studies designed to assess the delivery and quality of breast cancer screening and related patient outcomes in the United States. The BCSC is supported by grants and contracts from the Applied Research Program in NCI's Division of Cancer Control and Population Sciences.

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Genetic Variation in Inflammatory Pathways is Related to Colorectal Cancer Survival

Cornelia Ulrich

Polly Newcomb

Inflammation has been associated with the development of colorectal cancer and prognosis. This study is one of the first to investigate the relationship between inherited genetic polymorphisms (Prostaglandin synthase 1, PTGS-1, and IκBKβ) and survival of colorectal cancer. Both genes were associated with an altered risk of mortality from colorectal cancer.

Coghill AE, Newcomb PA, Poole EM, et al. Genetic variation in inflammatory pathways is related to colorectal cancer survivalExternal Web Site Policy. Clin Cancer Res. 2011 Nov 15;17(22):7139-47.

This research was supported in part by EGRP grants to Polly Newcomb, Ph.D., M.P.H.; and Cornelia Ulrich, Ph.D., both of the Fred Hutchinson Cancer Research Center.

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Clinically Relevant Updates in Family History of Cancer Needed Over Time

This study examined how often changes in family cancer history are great enough to warrant earlier or more intense screening for breast, colorectal, or prostate cancer. In order to maintain accurate family histories from their patients, physicians should get a comprehensive family history by age 30, and then update it every five to ten years because histories change significantly between 30 and 50 years of age. Obtaining updated histories every five years would maximize the likelihood of detecting cancer at an early, more treatable state.

  • Dianne Finkelstein

  • Hoda Anton-Culver

  • Jonathan Berg

  • Susan Domchek

  • Karen Edwards

  • Dierdre Hill

  • Claudine Isaacs

  • Anita Kinney

  • Jan Lowery

  • Patricia Moorman

  • Sharon Plon

  • Louise Strong

  • Argyrios Ziogas

Ziogas A, Horick NK, Kinney AY, et al. Clinically relevant changes in family history of cancer over timeExternal Web Site Policy. JAMA. 2011 Jul 13;306(2):172-8.

This research was supported in part by an EGRP contract and grants to the Cancer Genetics NetworkExternal Web Site Policy (CGN), including Dianne Finkelstein, Ph.D., of Harvard University and Massachusetts General Hospital; Hoda Anton-Culver, Ph.D., of the University of California, Irvine; Jonathan Berg, M.D., Ph.D., of the University of North Carolina at Chapel Hill; Deborah Bowen, Ph.D., of Boston University; Susan Domchek, M.D., of the University of Pennsylvania; Karen Edwards, Ph.D., of the University of Washington; Constance Griffin, M.D., of The Johns Hopkins University; Dierdre Hill, Ph.D., M.P.H., of the University of New Mexico Cancer Center; Claudine Isaacs, M.D., of Georgetown University; Anita Kinney, Ph.D., and Geraldine Mineau, Ph.D., of the Huntsman Cancer Institute; Jan Lowery, Ph.D., M.P.H., of the University of Colorado Denver; Patricia Moorman, Ph.D., M.S.P.H., and Joellen Schildkraut, Ph.D., M.P.H., of Duke Cancer Institute; Sharon Plon, M.D., Ph.D., of Baylor College of Medicine; Louise Strong, M.D., of The University of Texas MD Anderson Cancer Center; and Argyrios Ziogas, Ph.D., of the University of California, Irvine.

Constance Griffin
EGRP is deeply saddened by the recent passing of Dr. Griffin, who led The Johns Hopkins Kimmel Cancer Center's Cytogenetics Core and was director of the Pathology Molecular Diagnostics Laboratory. She was Co-Principal Investigator for the Mid-Atlantic CGN, funded by EGRP to promote cancer genetics research, education, and clinical services in the region and nationally. Dr. Griffin was a key member of CGN since its inception, and she will be missed. She published numerous articles on the importance of genetic findings in accurately diagnosing cancer. In recognition of her expertise, the College of American Pathologists selected Dr. Griffin's lab as a referee site to improve proficiency testing for cytogenetics, and she collaborated with renowned cancer researcher Bert Vogelstein, M.D., in developing a clinical test for the APC I1307K mutation associated with inherited colorectal cancer predisposition in Ashkenazi Jews.

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Genetic Map of African Americans Reveals Landscape of Recombination

Findings from this study represent the world's most detailed genetic map to date. While almost every genetic map built has been developed from people of European ancestry, this new one is the first constructed from African-American recombination genomic data. Interestingly, the positions where recombinations occur in African Americans are significantly different from non-African populations. This comprehensive map will help researchers understand the roots of diseases that occur more often in African Americans and to discover new disease-related genes in all populations through more precise gene mapping.

  • Christine

  • Christopher

  • William

  • Christopher

  • Brian

  • Jennifer

  • Esther

  • Lawrence

  • Ann

  • Margaret

  • John

  • Wei

Hinch AG, Tandon A, Patterson N, et al. The landscape of recombination in African AmericansExternal Web Site Policy. Nature. 2011 Jul 20;476:170-5.

This research was supported by EGRP grants to Christine Ambrosone, Ph.D., Roswell Park Cancer Institute; Christopher Amos, Ph.D., of The University of Texas MD Anderson Cancer Center; William Blot, Ph.D., of the International Epidemiology Foundation; Christopher Haiman, Sc.D., and Brian Henderson, M.D., both of the University of Southern California; Jennifer Hu, Ph.D., of the University of Miami Health System; Esther John, Ph.D., M.S.P.H., of the Cancer Prevention Institute of California; Lawrence Kolonel, M.D., Ph.D., of the University of Hawaii Cancer Center; Ann Schwartz, Ph.D., M.P.H., Wayne State University; Margaret Spitz, M.D., M.P.H., of the Baylor College of Medicine; John Witte, Ph.D., of the University of California, San Francisco; Wei Zheng, M.D., Ph.D., M.P.H., of Vanderbilt University.

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Principles Proposed for the Post-GWAS Functional Characterization of Cancer Risk Loci

The success of genome-wide association studies (GWAS) in identifying more than 200 common low-penetrance susceptibility loci for cancers presents a new challenge: understanding the role these regions play in cancer susceptibility. This publication - from a working group of the NCI-funded Genetic Associations and Mechanisms in Oncology (GAME-ON), a post-genome wide association initiative - suggests guidelines that can be used to advance the field from association of single nucleotide polymorphisms (SNPs) to understanding the cancer-causing potential of genetic variants. To date, the field has lacked principles for the identification of appropriate assays and models to test the cancer-causing effects of SNPs and genes mapping to cancer-related loci. Considering how to explore the functional impact [cancer-causing potential] of variants now will allow the scientific community to be well positioned to rise to the challenge of testing causation in the future.


  • Chris Carlson

  • Graham Casey

  • Gerhard Coetzee

  • Mariella De Biasi

  • Matthew Freedman

  • Simon Gayther

  • Michael James

  • Ian Mills

  • Alvaro Monteiro

  • Christoph Plass

  • Angela Risch

  • Jay Tichelaar

  • Haris Vikis

  • Ming You

Freedman ML, Monteiro AN, Gayther SA, et al. Principles for the post-GWAS functional characterization of cancer risk lociExternal Web Site Policy. Nat Genet. 2011 Jun;43(6): 513-8.

This research was supported by EGRP grants to Christopher Amos, Ph.D., of The University of Texas MD Anderson Cancer Center; Stephen Gruber, M.D., Ph.D., M.P.H., and Brian Henderson, M.D., of the University of Southern California; David Hunter, M.B.B.S., Sc.D., of Harvard University; and Thomas Sellers, Ph.D., M.P.H., H. Lee Moffitt Cancer Center & Research Institute.

GAME-ON, formerly called the Post-Genome Wide Association Initiative, brings together multidisciplinary teams of epidemiologists, basic scientists, and clinicians, to collaborate on investigating genomic regions that have been implicated in susceptibility to breast, colon, ovarian, prostate, and lung cancer.

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Incidence and Clearance of Human Papillomavirus Infection in Men AIDS Vaccination Modeling

Anna Giuliano

Little is known about the epidemiology of human papilloma virus (HPV) infection in men, making it difficult to identify the best prevention strategies. This prospective study provides data on incidence and clearance times of infection in men that are essential for development of realistic cost-effectiveness models for international male HPV vaccination.

Giuliano AR, Lee JH, Fulp W, et al. Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort studyExternal Web Site Policy. Lancet. 2011 Mar 12;377(9769):932-40.

This research was supported by an EGRP grant to Anna Giuliano, Ph.D., of the H. Lee Moffitt Cancer Center & Research Institute.

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Integrative Genomics Identifies Neuroblastoma Oncogene

John Maris

Neuroblastoma accounts for about 10% of all childhood cancer deaths. This study found that polymorphisms at the LMO1 locus are strongly associated with susceptibility for this cancer and the likelihood of further somatic alterations at this locus leading to malignant progression.

Wang K, Diskin SJ, Zhang H, et al. Integrative genomics identifies LMO1 as a neuroblastoma oncogeneExternal Web Site Policy. Nature. 2011 Jan 13;469(7329):216-20.

This research was supported by an EGRP grant to John Maris, M.D., of The Children's Hospital of Philadelphia.

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New Clues Provided for Prostate Cancer Risk and Pesticide Exposure

Myles Cockburn

Few established risk factors for prostate cancer exist. Previous research indicates agricultural exposures play a role in prostate cancer in agricultural workers. This new study focused on ambient residential pesticide exposures in agriculturally intensive areas in California. A strong association was found between prostate cancer risk and exposure to methyl bromide and a group of organochlorines.

Cockburn M, Mills P, Zhang X, et al. Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in CaliforniaExternal Web Site Policy. Am J Epidemiol. 2011 Jun 1;173(11):1280-8.

This research was supported by an EGRP grant to Myles Cockburn, Ph.D., of the University of Southern California.

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Congenital Anomalies in the Children of Cancer Survivors

John Boice, Jr.

This study is among the largest studies of congenital anomalies in the offspring of childhood cancer survivors and the first to study anomalies using quantified gonadal radiation doses. The children of 5-year cancer survivors did not appear to be at increased risk for congenital anomalies based on their parent's exposure to mutagenic treatments.

Signorello et al. Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor StudyExternal Web Site Policy. J Clin Oncology. 2012 Jan 20;30(3):239-45. Epub 2011 Dec 12.

This research was supported by an EGRP grant to John Boice, Jr., Sc.D., of Vanderbilt University.

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