Association of CYP19A1 polymorphisms with risks for atypical adenomatous hyperplasia and bronchioloalveolar carcinoma in the lungs

• Published in: Carcinogenesis (New York) Vol. 31; no. 10; pp. 1794 - 1799
• Main Authors: Kohno, Takashi, Kakinuma, Ryutaro, Iwasaki, Motoki, Yamaji, Taiki, Kunitoh, Hideo, Suzuki, Kenji, Shimada, Yoko, Shiraishi, Kouya, Kasuga, Yoshio, Hamada, Gerson Shigeaki, Furuta, Koh, Tsuta, Koji, Sakamoto, Hiromi, Kuchiba, Aya, Yamamoto, Seiichiro, Kanai, Yae, Tsugane, Shoichiro, Yokota, Jun
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-10-2010
• Subjects: Adenocarcinoma, Bronchiolo-Alveolar - blood; Adenocarcinoma, Bronchiolo-Alveolar - etiology; Adenocarcinoma, Bronchiolo-Alveolar - genetics; Adult; Aged; Aromatase - genetics; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Estrogens - blood; Female; Humans; Hyperplasia; Lung - pathology; Lung Neoplasms - blood; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Male; Medical sciences; Middle Aged; Pneumology; Polymorphism, Single Nucleotide; Precancerous Conditions - blood; Precancerous Conditions - etiology; Precancerous Conditions - genetics; Risk Factors; Smoking - adverse effects; Tumors; Tumors of the respiratory system and mediastinum; Lung disease; Genetic variability; Enzyme; Respiratory disease; Lung cancer; Cytochrome P450; Hyperplasia; Lung; Genotype; Malignant tumor; Respiratory system; Association; Risk factor; Bronchus disease; Cytochrome P450 19A1; Atypical; Cancer; Bronchioloalveolar carcinoma; Polymorphism
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgq159

Estrogen has been indicated to play an etiological role in the development of lung adenocarcinoma (ADC), particularly bronchioloalveolar carcinoma (BAC), a type of ADC that develops from a benign adenomatous lesion, atypical adenomatous hyperplasia (AAH). Polymorphisms in the CYP19A1 gene cause interindividual differences in estrogen levels. Here, 13 CYP19A1 single-nucleotide polymorphisms (SNPs) were examined for associations with lung AAH risk. AAH is detected as ground-glass opacity (GGO) by computed tomography (CT) examination, and this study consisted of 100 individuals diagnosed with GGO in their lungs among 3088 CT-based cancer screening examinees and 424 without. Minor allele carriers for the rs3764221 SNP showed an elevated risk for GGO [odds ratio (OR) = 1.72, P = 0.017]. Associations of this SNP with risks for lung AAH and BAC in the lungs were next examined using 359 ADC cases whose resected lung lobes were subjected to a histological examination for AAH accompaniment and the presence of BAC components and 330 controls without cancer. The ORs were also increased for lung ADC accompanied by AAH (OR = 1.74, P = 0.029) as well as lung ADC with BAC components (OR = 1.41, P = 0.091). The minor allele was associated with an increased circulating estradiol level (P = 0.079) in a population of 363 postmenopausal women without cancer. These results indicate that CYP19A1 polymorphisms are involved in the risk for lung AAH and BAC in the lungs by causing differences in estrogen levels.