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  • American Association for Cancer Research (AACR)  (5)
  • Chen, Ken-Chung  (5)
  • Weng, Ya-Ling  (5)
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  • American Association for Cancer Research (AACR)  (5)
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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4145-4145
    Abstract: Background: Although most cases of head and neck cancer (HNC) can be attributed to three established risk factors, including alcohol, betel quid, and cigarette, the underlying genetic variations among individuals may be important in modulating the risk of HNC. Previous studies showed that the metabolism or function of retinoic acid may be modified by the use of alcohol, betel quid, or cigarette, resulting in the dysregulation of cell growth, differentiation, and apoptosis. The current analysis examined the association between HNC risk and genetic polymorphisms of genes on the retinoic acid pathway. Methods: 408 incident cases of HNC and 473 sex- and age- frequency matched controls were recruited from the department of otolaryngology and department of stomatology. Information on the use of alcohol, betel quid, and cigarette was collected by in-person interviews. In the discovery phase, 223 cases and 220 controls were genotyped for 368 single nucleotide polymorphisms (SNPs) of 37 retinoic acid genes. Unconditional logistic regression was performed to estimate the log-additive odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with each SNP. Those that had a P & lt; 0.05 were further genotyped for 185 cases and 253 controls in stage 2. Additional analyses were performed stratified by alcohol, betel quid, and cigarette to evaluate gene-environment interaction. Results: In the stage 1, 25 SNPs were associated with the risk of HNC with a P & lt; 0.05. With additional genotyping performed for these 25 SNPs in stage 2, only one SNP of RARB showed a decreasing P value with additional samples (stage 1 OR = 1.43, 95% CI: 1.02-2.00, P = 0.04; stage 2 OR = 1.33, 95% CI: 0.94-1.89, P = 0.1; combined OR = 1.34, 95% CI: 1.06-1.69, P = 0.01). In addition, the association between this RARB SNP and HNC risk appeared to be modified by alcohol drinking status. A positive association between the minor allele of the RARB SNP and HNC was observed among never drinkers (OR = 1.96, 95% CI: 1.30-2.95) but not among ever drinkers (OR = 1.09, 95% CI: 0.81-1.47) (P for interaction = 0.01). Conclusion: The risk of HNC was associated with a SNP of RARB and this association appeared to depend on alcohol drinking status. Further investigations are needed to determine the causal SNP and its functional significance. Citation Format: Jeffrey S. Chang, Jenn-Ren Hsiao, Jang-Yang Chang, Tung-Yiu Wong, Sen-Tien Tsai, Chun-Yen Ou, Hung-I Lo, Sheen-Yie Fang, Cheng-Chih Huang, Wei-Ting Lee, Jiunn-Liang Wu, Ken-Chung Chen, Jehn-Shyun Huang, Yi-Hui Wang, Ya-Ling Weng, Han-Chien Yang. Genetic polymorphisms of genes on the retinoic acid pathway and risk of head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4145. doi:10.1158/1538-7445.AM2014-4145
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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    detail.hit.zdb_id: 410466-3
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  • 2
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 28, No. 2 ( 2019-02-01), p. 248-257
    Abstract: Although alcohol drinking is an established risk factor of head and neck cancer (HNC), less is known about its role in the prognosis of HNC. The current study investigated the association between pretreatment alcohol consumption and the overall survival (OS) of HNC patients. Methods: Cox proportional hazards models were performed to evaluate the association between prediagnosis alcohol drinking and the OS of HNC patients. In addition, the influence of the polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on this relationship was also evaluated. Results: The results showed a significant positive dose–response relationship between prediagnosis alcohol use and worse OS of HNC patients. This association was more significant for oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer than for oral cancer. The association between alcohol use and the poorer OS of HNC patients was mainly through its association with a higher stage of HNC at diagnosis. The worst OS associated with alcohol use was observed among HNC patients with the fast ADH1B and the slow/nonfunctional ALDH2 genotype combination. Conclusions: Our analysis showed a significant positive dose–response relationship between prediagnosis alcohol use and a worse OS of HNC. This association was mainly due to the higher stage of HNC among alcohol drinkers. In addition, the polymorphisms of the ethanol-metabolizing genes, ADH1B and ALDH2, modified the relationship between prediagnosis alcohol use and the OS of HNC patients. Impact: Prediagnosis alcohol use may be a prognostic indicator of HNC.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036781-8
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 105-105
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 105-105
    Abstract: Background: Head and neck cancer (HNC), including cancer of the oral cavity, pharynx, and larynx, is one of the leading cancers in the world. The known risk factors, including alcohol, betel quid, and cigarette, account for the majority of the HNC cases. However, the biological mechanisms regarding the carcinogenic effects of these agents in the development of HNC are not completely understood. Retinoic acid is involved in cell growth, differentiation, and apoptosis, which when dysregulated may lead to the development of cancer. Studies have shown that alcohol, betel quid, and cigarette can affect either the metabolism or the function of retinoic acid pathway. The current analysis evaluated the association between serum retinol and HNC risk and assessed whether this association can be modified by alcohol, betel quid, or cigarette. Methods: 93 incident cases of HNC and 79 sex- and age- frequency matched controls were recruited from the department of otolaryngology and department of stomatology. Information on the use of alcohol, betel quid, and cigarette was collected by in-person interviews. Serum retinol levels were measured using high performance liquid chromatography. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with serum retinol levels. Additional analyses were performed stratified by alcohol, betel quid, and cigarette. Results: Compared to controls, HNC cases had a lower level of serum retinol (Median for HNC cases: 811 ug/l vs. median for controls: 901 ug/l, Wilcoxon rank-sum P = 0.04). For every 100 ug/l increase, the risk of HNC was reduced by 8% (OR = 0.92, 95% CI: 0.83-1.02). The OR was 0.5 (95% CI: 0.24-1.06) comparing the highest tertile of serum retinol level to the lowest tertile. A lower HNC risk associated with higher serum retinol levels was observed among never alcohol drinkers (For every 100 ug/l increment, OR = 0.80, 95% CI: 0.66-0.96) but not among regular alcohol drinkers (For every 100 ug/l increment, OR = 0.98, 95% CI: 0.86-1.13). Conclusion: Higher levels of serum retinol are associated with a reduced risk of HNC. Alcohol consumption obliterates the inverse association between serum retinol and HNC risk, possibly by disrupting the metabolism of retinoic acid pathway. Citation Format: Jeffrey S. Chang, Jenn-Ren Hsiao, Chun-Yen Ou, Tung-Yiu Wong, Sen-Tien Tsai, Hung-I Lo, Cheng-Chih Huang, Wei-Ting Lee, Ken-Chung Chen, Jehn-Shyun Huang, Yi-Hui Wang, Ya-Ling Weng, Han-Chien Yang. Serum retinol and risk of head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 105. doi:10.1158/1538-7445.AM2013-105
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2627-2627
    Abstract: Background: Retinoic acid is important for cell growth, differentiation, and apoptosis, which when dysregulated may predispose the development of cancer. Retinoic acid metabolism can be influenced by ethanol, cigarette smoking, and areca nut, the three major risk factors of head and neck cancer (HNC). A previous genome-wide association study reported an association between serum retinol level and two single nucleotide polymorphisms (SNPs) in two retinol transporter genes (TTR rs1667255 and RBP4 rs10882272) (1). The current study assesses the association between these two SNPs and HNC risk. Methods: 133 incident cases of HNC and 128 sex- and age- matched controls were recruited from the department of otolaryngology and department of stomatology. Data on the use of alcohol, cigarette, and areca nut were ascertained through in-person interview. Genotyping of TTR rs1667255 and RBP4 rs10882272 was performed using the Taqman-based real-time PCR method. Unconditional logistic regression was performed to estimate HNC risk associated with the two SNPs. Results: No association between HNC risk and TTR rs1667255 or RBP4 rs10882272 was observed. However, the two SNPs appeared to modify the relationship between alcohol consumption and HNC risk. There was an increased risk of HNC associated with daily alcohol drinking only among subjects with the “high serum retinol genotypes” (CC for TTR rs1667255: odds ratio (OR) = 4.6, 95 confidence interval (CI): 1.3-16.3; TT for RBP4 rs10882272: OR = 2.3, 95% CI: 1.2-4.4). While daily alcohol drinking was not associated with an increased risk of HNC among subjects with the “low serum retinol genotypes” (AA or AC for TTR rs1667255: OR = 1.4, 95% CI: 0.7-2.9; TC or CC for RBP4: OR = 0.7, 95% CI: 0.1-3.6). Conclusion: The association between alcohol consumption and HNC risk is modified by the polymorphisms of retinol transporter genes. Reference: 1. Mondul AM, Yu K, Wheeler W, et al. Genome-wide association study of circulating retinol levels. Human molecular genetics 2011;20:4724-31. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2627. doi:1538-7445.AM2012-2627
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 11_Supplement ( 2012-11-01), p. 15-15
    Abstract: Background: Alcohol is a major risk factor for head and neck cancer (HNC). The metabolism of ethanol can disrupt the metabolism of retinoic acid because the two pathways share some key enzymes. Retinoic acid is involved in cell growth, differentiation, and apoptosis, which when dysregulated may lead to the development of cancer. A previous genome-wide association study reported an association between single nucleotide polymorphisms (SNPs) in two retinol transporter genes (TTR and RBP4) and serum retinol level (1). The current study evaluates the interaction between alcohol consumption and SNPs in TTR and RBP4 on the risk of HNC. Methods: 223 incident cases of HNC and 214 sex- and age- matched controls were recruited from the department of otolaryngology and department of stomatology. In-person interviews were conducted to collect information on the use of alcohol, cigarette, and betel quid. Three tag-SNPs of TTR and 8 tag-SNPs of RBP4 were genotyped using the Taqman-based real-time PCR method or mass spectrometry-based detection method. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with each SNP and to evaluate the joint influence of SNPs and alcohol consumption on HNC risk, adjusted for age, sex, education, cigarette smoking and betel quid use. Results: No significant association between HNC risk and any of the 11 tag-SNPs was observed. However, three SNPs of RBP4 appeared to modify the relationship between alcohol consumption and HNC risk. After combining the three SNPs into a polygenic risk score, the results showed that those who drank alcohol daily had a different risk of HNC, depending on the number of variant alleles (0 to 2 variant alleles: OR=1.2, 95% CI: 0.7-2.1; 3 or more variant alleles: OR=2.9, 95% CI: 1.1-7.9; interaction P-value = 0.01) Conclusion: The association between HNC risk and alcohol consumption is modified by the polymorphisms of RBP4. Citation Format: Jeffrey S. Chang, Jenn-Ren Hsiao, Tung-Yiu Wong, Sen-Tien Tsai, Chun-Yen Ou, Hung-I Lo, Cheng-Chih Huang, Wei-Ting Lee, Ken-Chung Chen, Jehn-Shyun Huang, Yi-Hui Wang, Ya-Ling Weng, Han-Chien Yang. Interaction between retinol transporter genes and alcohol on the risk of head and neck cancer. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 15.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Location Call Number Limitation Availability
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