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Articles by J. Yokota
Total Records ( 2 ) for J. Yokota
  T Kohno , H Kunitoh , Y Shimada , K Shiraishi , Y Ishii , K Goto , Y Ohe , Y Nishiwaki , A Kuchiba , S Yamamoto , H Hirose , A Oka , N Yanagitani , R Saito , H Inoko and J. Yokota
 

Adenocarcinoma (ADC) is the commonest histological type of lung cancer, and its weak association with smoking indicates the necessity to identify high-risk individuals for targeted screening and/or prevention. By a genome-wide association study (GWAS), we identified an association of polymorphisms in the 6p21.31 locus containing four human leukocyte antigen (HLA) class II genes with lung ADC risk. DQA1*03 of the HLA-DQA1 gene was defined as a risk allele with odds ratio (OR) of 1.36 [95% confidence interval (CI) = 1.21–1.54, P = 5.3 x 10–7] by analysis of 1656 ADC cases and 1173 controls. DQA1*03 and the minor allele for a polymorphism, rs2736100, in TERT, another lung cancer susceptibility locus identified in recent GWASs on Europeans and Americans, were indicated to independently contribute to ADC risk with per allele OR of 1.43 (95% CI = 1.31–1.56, P = 7.8 x 10–16). Individuals homozygous both for the DQA1*03 and minor TERT alleles were defined as high-risk individuals with an OR of 4.76 (95% CI = 2.53–9.47, P = 4.2 x 10–7). The present results indicated that individuals susceptible to lung ADC can be defined by combined genotypes of HLA-DQA1 and TERT.

  T Kohno , R Kakinuma , M Iwasaki , T Yamaji , H Kunitoh , K Suzuki , Y Shimada , K Shiraishi , Y Kasuga , G. S Hamada , K Furuta , K Tsuta , H Sakamoto , A Kuchiba , S Yamamoto , Y Kanai , S Tsugane and J. Yokota
 

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.

 
 
 
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