Biography

I have worked at the National Cancer Institute, managing and coordinating genomic and cancer epidemiologic research in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. As a cancer epidemiologist, my research focuses on genetic, epigenetic, serum, and tissue markers in DNA repair, metabolic, infection, and inflammatory pathways as they relate to the risk of colorectal and other cancers.

1. Generating and managing the PLCO resource. Huang serves in the steering and management team of the PLCO trial. The trial has collected data and biospecimens for >150,000 participants since 1993 and has become a valuable and heavily used resource for the research community. The PLCO Atlas GWAS Explorer project led by Dr. Huang and colleagues in NCI has created a large public resource of genotype data for >110,000 cohort members and genome-wide association studies (GWAS) results for >90 cancer and related traits. The >1400 published research findings from the PLCO to date have led to major advances in the understanding of cancer.

2. Colorectal cancer etiology, genetic determinants, tumor sub-types and epigenetic alterations: Dr. Huang published a study of leukocyte genomic methylation and colorectal cancer, suggesting that adequate folate status may protect against the disease through mechanisms involving adequate DNA methylation in the genome. Dr. Huang has collaborated with the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) on a targeted sequencing project to comprehensively characterize somatic mutations of colorectal tumor tissues. Besides epigenetic and pathomolecular markers, Dr. Huang brought together NCI and GECCO investigators to study the utility of polygenic risk score (PRS) for personalized surveillance decisions, improved risk prediction of adenoma incidence and recurrence, and its interrelationship with lifestyle risk factors for colorectal cancer. Furthermore, Dr. Huang coordinates a working group among NCI and external collaborators to conduct a series of studies on etiology of prevalent, incident, and recurrent adenoma and colorectal cancer in the PLCO, investigating the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) use, obesity, lifetime alcohol drinking patterns, and dietary factors across the stages of colorectal cancer development. For example, they found that obesity is important throughout all stages of the colorectal adenoma-cancer progression; regular screening and detection and removal of colorectal adenomas does not eliminate the risk of colorectal cancer associated with obesity. They also found a beneficial role for not only aspirin, but also ibuprofen, in preventing advanced adenoma and curbing progression to recurrence and cancer in this elderly population.

3. Smoking-related colorectal adenoma risk modifications by polycyclic aromatic hydrocarbons (PAH) metabolism genes: Dr. Huang and colleagues found that smoking is associated with adenoma risk with clear dose-dependent trends in smoking frequency, duration, and recency. Dr. Huang and colleagues further found smoking-related adenoma risk modifications by variants of PAH metabolism genes, including EPHX1, NQO1, CYP1A1, and GSTT1, suggesting the importance of genetic susceptibility in tobacco-related colorectal carcinogenesis.

4. DNA repair genetic variants and susceptibility to cancer outcomes: Prior to the GWAS era, Dr. Huang published a series of papers evaluating DNA repair gene variants in relation to risks of several cancers. Investigating more than 150 genes in the nucleotide excision repair, base excision repair, and other DNA repair pathways, Dr. Huang et al. found that XPC, APEX1, XRCC1, PARP1, EXO1 and ATM variants may be associated with advanced colorectal adenoma. Pooling data and specimens from three case-control studies of head and neck cancer in Washington State, North Carolina, and Puerto Rico, Dr. Huang et al. found that MGMT variants may be associated with disease risk. Dr. Huang’s findings on gastric cancer, biliary tract cancer, and prostate cancer also led to important follow-ups in subsequent studies.

5. Sexually transmissible infections (STIs), inflammation markers, and genetics in relation to prostate cancer risk: Dr. Huang led an investigation to evaluate prostate cancer risk associated with serology of Chlamydia trachomatis, HPV types 16 & 18, HSV type 2, CMV, and HHV-8, and self-report history of syphilis and gonorrhea, and found a borderline association for any STI versus none, suggesting that a shared response or correlated infection not directly measured may underlie the moderate association. She and colleagues then conducted several studies on inflammation-related factors and prostate cancer. They found evidence of higher IL-16 level associated with increased risk of high-grade disease, and daily aspirin use associated with modest protection against the disease, supporting inflammation as potential mechanism by which STIs may increase risk.