CONTROL ID: 2997739 PRESENTATION TYPE: Oral
TITLE: Polymorphisms of genes related to nucleotide excision repair and cell cycle pathways, arsenic exposure, and bladder cancer
AUTHORS (LAST NAME, FIRST NAME): Cheng, Ya-Yun1; Guo, How-Ran1 INSTITUTIONS (ALL):
1. Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan. COMMUNICATING AUTHOR:
Ya-Yun Cheng : Selected PRESENTER: Ya-Yun Cheng ABSTRACT BODY:
Abstract: Arsenic is a human carcinogen, and previous studies have demonstrated that it may act through the inhibition of DNA repair mechanisms and the disruption of mitosis to induce apoptosis and centrosome aneuploidy. DNA adducts caused by chemical carcinogens are repaired primarily through the nucleotide excision repair (NER) pathway. Aneuploidy is a common phenomenon regulated by Aurora A (STK15) in cancer cells. The tumor suppressor p53 is an important regulator of the cell cycle and apoptosis and is frequently inactivated in human cancers. We conducted a study in southwestern Taiwan to evaluate whether genetic polymorphisms in the NER (ERCC1 Asn118 Asn, XPD Lys751Gln, and XPC Ala499Val) and cell cycle (functional STK15 Phe31Ile and p53 Pro72Arg) pathways have associations with bladder cancers related to arsenic exposure. We recruited 104 bladder cancer patients and 265 cancer-free controls. A questionnaire was used to collect data on demographics, life style, and environmental factors. Genotypes were determined using PCR-RFLP. The arsenic level in drinking water of each participant was assessed on the basis of the address. We found that older age, male sex, lower education level, smoking, and arsenic exposure (with dose-response relationship, p<0.05 for test for trend) were risk factors of bladder cancer. Among the NER pathway polymorphisms, we found ERCC1 Asn118Asn was associated with bladder cancer (odds ratio [OR] = 5.4; 95% confidence interval [CI]: 2.7-11.0) after adjusting for the arsenic level in drinking water and other risk factors. Among the cell cycle pathway polymorphisms, we found STK15 Phe31Ile (T>A) mutant type (AA) (OR=2.7; 95% CI: 1.1-7.1) was associated with a higher risk of bladder cancer.
KEYWORDS: Arsenic Exposure and Health, Gene-environment Interactions, Cancer and Environment, X - Other (enter below), X - Other (enter below).
Other Keyword: DNA repair, NER pathway, bladder cancer Award Consideration: Yes
Student or Early researcher: Early Career Researcher (less than five years post PhD or terminal degree) Abstract - Original Information: The research described in this abstract has not been previously published or presented.
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