Sylvester Comprehensive Cancer Center

Jennifer J. Hu, Ph.D.

Jennifer J. Hu, Ph.D.

Professor of Epidemiology & Public Health; Associate Director for Cancer Prevention and Control, Sylvester Comprehensive Cancer Center

Description of Research

Considerable evidence associates DNA damage/repair with human cancer risk and progression. However, conducting a large population screening for every susceptibility gene is not yet feasible (e.g., DNA repair), and so the contribution of DNA-repair genetic variants to repair function and human cancer risk/progression is still unclear. Dr. Hu has evaluated the application of several DNA-repair functional assays in human cancer risk assessment. Results show that DNA damage and repair play important roles in human carcinogenesis and progression. Since multiple DNA repair pathways are required to maintain genome integrity, and many genes are involved in different repair pathways, genetic defects in multiple DNA repair genes have additive or multiplicative effects on repair functions and human cancer risk/progression.

Genotypes and phenotypes in different repair pathways must be evaluated simultaneously in order to fully assess their impact on human cancer susceptibility and progression. The functional significance of DNA-repair single nucleotide polymorphisms (SNPs) and human cancer risk/progression is currently the subject of intense study, and many challenges must be overcome. With the rapid improvement of high-throughput genotyping methods, we will be able to rapidly translate genetic susceptibility information into health behavior promotion; because genetically susceptible (sub)populations are more motivated to seek screening and intervention. However, investigating whether specific variants may alter DNA repair function, while evaluating their application as cancer susceptibility/progression markers, is crucial to reaching this goal. Dr. Hu's research program focuses on genetic polymorphisms of DNA repair in human cancer risk assessment and prevention (i.e. breast cancer, prostate cancer, and colon cancer). The central theme of this research is built on the concept that both genetic (i.e. race, family history of cancer, and genetic polymorphisms) and non-genetic factors (i.e. aging, oxidative stress, and exposure) may contribute to cancer risk and progression. Dr. Hu's laboratory is currently conducting several cancer case-control and case-only studies to test several hypotheses as follows:

1. To test whether human cancer risk/progression is associated with specific DNA repair SNPs with amino acid substitutions in 4 different repair pathways: (1) base excision repair (BER), (2) nucleotide excision repair (NER), (3) double strand break repair (DSBR), and (4) mismatch repair (MRR).

2. To evaluate whether genetic variants of DNA repair genes result in defective repair and elevated DNA damage. Four functional assays will be used: the Double Mismatch Reversion (DMR) assay for BER, the DNA repair Capacity (DRC) assay for NER, the cell-cycle G2 delay assay for ionizing-radiation sensitivity, and the Comet assay for DNA damage.

3. To elucidate the molecular mechanisms of gene-gene and gene-environment interactions in human cancer risk and progression. Since genotypes are not modifiable, this approach aims to identify environmental risk factors that are amenable to intervention (e.g., diet, lifestyle, and other exposures), particularly in genetically susceptible (sub)populations and cancer survivors.

To provide an effective etiology-based strategy for cancer prevention, the long-term objectives are: (i) to evaluate the roles of DNA repair in human cancer risk and progression, (ii) to characterize the genetic/non-genetic regulations of DNA repair in cancer susceptibility and progression, (iii) to identify high-risk populations by using validated biomarkers, and (iv) to reduce cancer risk and increase survival by targeting modifiable risk/prognostic factors.


  • Found that deficient DNA repair and elevated DNA damage are associated with human breast cancer risk; women with XRCC1 and APE1 variant alleles are hypersensitive to ionizing radiation (IR); and women with XRCC1 and XRCC3 variant alleles have significantly increased risk for breast cancer compared to women with wild-type alleles for both genes.
  • Observed black-white differences in genotypes and exposures, and potential gene-gene and gene-environment interactions in colon cancer risk.

Selected Cancer-Related Publications

  • Lewis JE, Soler-Vilá H, Clark PE, Kresty La, Allen GO, Hu JJ. Intake of plant foods and associated nutrients in prostate cancer risk. Nutr Cancer 61:216-24,2009. Read more »
  • Xu J, Kibel AS, Hu JJ, Turner AR, Pruett K, Zheng SL, Sun J, Isaacs SD, Wiley KE, Kim ST, Hsu FC, Wu W, Torti FM, Walsh PC, Chang BL, Isaacs WB. Prostate cancer risk associated loci in African Americans. Cancer Epidemiol Biomarkers Prev 18:2145-9, 2009. Read more »
  • Nieder AM, MacKinnon JA, Fleming LE, Kearney G, Hu JJ, Sherman RL, Huang Y, Lee DJ. Bladder cancer clusters in Florida: identifying populations at risk. J Urol 182:46-50; discussion 51, 2009. Read more »
  • Zabaleta J, Su LJ, Lin HY, Sierra RA, Hall MC, Sartor AO, Clark PE, Hu JJ, Ochoa AC. Cytokine genetic polymorphisms and prostate cancer aggressiveness. Carcinogenesis 30:1358-62, 2009. Read more »


Collaborating in the Multidisciplinary Research Program(s):

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