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Etiology of lung cancer and environm...

Hosgood, Howard Dean, III.

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Etiology of lung cancer and environmental risk factors in Xuanwei, China.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Etiology of lung cancer and environmental risk factors in Xuanwei, China./
作者:	Hosgood, Howard Dean, III.
面頁冊數:	260 p.
附註:	Adviser: Tongzhang Zheng.
Contained By:	Dissertation Abstracts International69-05B.
標題:	Environmental Sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3317130
ISBN:	9780549658733

Etiology of lung cancer and environmental risk factors in Xuanwei, China.
Hosgood, Howard Dean, III.

Etiology of lung cancer and environmental risk factors in Xuanwei, China. - 260 p.

Adviser: Tongzhang Zheng.

Thesis (Ph.D.)--Yale University, 2008.

Globally, lung cancer accounts for 1.4 million cancer cases and 1.2 million cancer deaths per year. While smoking is the primary risk factor, domestic fuel combustion from cooking and heating, which about 3 billion people are exposed to worldwide, is also associated with lung cancer risk. Xuanwei has provided a unique opportunity to study in-home coal smoke because it has the highest lung cancer incidence in China, with the attributable risk of lung cancer from unvented smoky coal burning >90%, and nearly all women and few men cook, while most men and nearly no women smoke tobacco.

ISBN: 9780549658733Subjects--Topical Terms:

676987
Environmental Sciences.

Etiology of lung cancer and environmental risk factors in Xuanwei, China.
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100 1 $a Hosgood, Howard Dean, III. $3 1279382
245 1 0 $a Etiology of lung cancer and environmental risk factors in Xuanwei, China.
300 $a 260 p.
500 $a Adviser: Tongzhang Zheng.
500 $a Source: Dissertation Abstracts International, Volume: 69-05, Section: B, page: 2886.
502 $a Thesis (Ph.D.)--Yale University, 2008.
520 $a Globally, lung cancer accounts for 1.4 million cancer cases and 1.2 million cancer deaths per year. While smoking is the primary risk factor, domestic fuel combustion from cooking and heating, which about 3 billion people are exposed to worldwide, is also associated with lung cancer risk. Xuanwei has provided a unique opportunity to study in-home coal smoke because it has the highest lung cancer incidence in China, with the attributable risk of lung cancer from unvented smoky coal burning >90%, and nearly all women and few men cook, while most men and nearly no women smoke tobacco.
520 $a To determine whether lung cancer mortality decreased after changing from unvented stoves to portable stoves, lifetime smoky coal users were evaluated in an extended follow-up (1976-1996) of the Xuanwei cohort. In total, 4,054 (78195.9 person-years) lifetime smoky coal users changed to portable stoves, 4,364 (60322.8 person-years) did not undergo stove improvement, and 1,074 died of lung cancer. Sex-specific Cox regression models found portable stoves were associated with decreased lung cancer mortality in males (Hazard Ratio (HR) = 0.6, 95% Confidence Interval (CI) = 0.5-0.8) and females (HR = 0.4, CI = 0.3-0.6), after adjustment for potential confounders. This is the first report showing that portable stove use reduces lung cancer mortality, highlighting a cost-effective intervention opportunity with the power to substantially benefit health in developing countries.
520 $a To explore the role of genetic predisposition and lung cancer in Xuanwei, a large-scale pathway-based candidate gene evaluation in a population-based case-control study (122 cases; 111 controls) evaluated a total of 1260 single nucleotide polymorphisms (SNPs) in 380 candidate genes for cancer. Genes were assigned to one of ten pathways based on gene ontology. Pathway analysis by a test for proportions identified the cell cycle pathway as most important (p = 0.044). Nine genes were significantly associated with lung cancer by the permutation test (PLA2G6 p = 0.001, CCNA2 p = 0.006, GSK3beta p=0.007, AKT1 p=0.010, EGF p=0.013, TP53I3 p=0.017, PTEN p=0.018, MYBL2 p = 0.033 and CCND3 p = 0.038) in the cell cycle pathway after accounting for multiple comparisons. Logistic regression for individual SNPs identified the most important variant of each gene (AKT1 rs1130233, CCNA2 rs3217773, CCND3 rs9529, EGF rs2237051, GSK3beta rs6781942, MYBL2 rs285164, PLA2G6 rs84473, PTEN rs1903858, and TP53I3 rs4149371). Cell cycle disruption enables cancer cells to avoid apoptosis. Significant genes were concentrated in the AKT pathway, which regulates cell cycle progression and apoptosis. Our findings suggest that genetic variation in the cell cycle pathway may be important in lung cancer etiology in Xuanwei.
520 $a Finally, two meta-analyses were performed on genotypes frequently associated with lung cancer. Six studies (912 cases; 1063 controls) in Asian populations with substantial indoor air pollution from heating and cooking evaluating xenobiotic detoxifying glutathione S-transferases (GSTM1, GSTT1, GSTP1 ) found GSTM1 null to be associated with lung cancer risk (odds ratio (OR) = 1.3; CI, 1.0-1.8), particularly in coal using populations (OR = 1.6; CI = 1.3-2.1). Seven studies (4276 cases; 5022 controls) evaluating the cell cycle regulator MDM2 309 T>C (rs2279744), also found an increased risk of lung cancer (ORCC=1.3, CI = 1.0-1.7), particularly in adenocarcinomas (OR = 1.9, CI = 1.4-2.5) and Asians (OR = 1.4, CI = 1.0-1.8).
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