Dataset Information

CLPTM1L genetic polymorphisms and interaction with smoking and alcohol drinking in lung cancer risk: a case-control study in the Han population from northwest China.

ABSTRACT: Genetic variants of cleft lip and palate trans-membrane 1-like (CLPTM1L) genes in the p15.33 region of chromosome 5 were previously identified to influence susceptibility to lung cancer. We examined the association of single nucleotide polymorphisms (SNPs) in CLPTM1L genes with lung cancer and explored their potential effects on the relationship between environmental risk factors (smoking, drinking) and lung cancer in a Chinese Han population. We genotyped 9 single nucleotide polymorphisms (SNPs) of CLPTM1L in a case-control study with 228 lung cancer cases and 301 controls from northwest China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. We identified that the minor alleles of rs451360, rs402710, and rs31484 in CLPTM1L were associated with a 0.52-fold, 0.76-fold, and 0.70-fold decreased risk of lung cancer in allelic model analysis, respectively. In the genetic model analysis, we found rs402710 and rs401681 were associated with decreased lung cancer risk. Further stratification analysis showed that rs380286 displayed a significantly decreased lung cancer risk (OR=0.65, P=0.041) in the non-drinkers. In addition, Haplotype "GTTATCTGT" was found to be associated with decreased lung cancer risk (OR=0.50, P=0.033). Our results verified that genetic variants of CLPTM1L contribute to lung cancer susceptibility in the northwest Chinese Han population. Additionally, we found that consumption of alcohol may interact with CLPTM1L polymorphisms to contribute to overall lung cancer susceptibility.

SUBMITTER: Xun X

PROVIDER: S-EPMC4603120 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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CLPTM1L genetic polymorphisms and interaction with smoking and alcohol drinking in lung cancer risk: a case-control study in the Han population from northwest China.

Xun Xiaojie X Wang Huijuan H Yang Hua H Wang Hong H Wang Bo B Kang Longli L Jin Tianbo T Chen Chao C

Medicine 20141201 28

Genetic variants of cleft lip and palate trans-membrane 1-like (CLPTM1L) genes in the p15.33 region of chromosome 5 were previously identified to influence susceptibility to lung cancer. We examined the association of single nucleotide polymorphisms (SNPs) in CLPTM1L genes with lung cancer and explored their potential effects on the relationship between environmental risk factors (smoking, drinking) and lung cancer in a Chinese Han population. We genotyped 9 single nucleotide polymorphisms (SNPs ...[more]

PMID: 25526467

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Project description:BACKGROUND: Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk. METHODS: We evaluated the role of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P < 0.01) while the A1298C polymorphism was not associated with lung cancer risk. The minor alleles of both polymorphisms behaved in a recessive fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking). CONCLUSIONS: The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the MTHFR polymorphisms in lung cancer development.

Project description:BACKGROUND:To assess the association of the interaction between the rs9619311 and rs402007 polymorphisms and smoking with essential hypertension (EH) in a Chinese Han population. METHOD:Peripheral blood samples were extracted from 422 EH patients and 280 normotensive (NT) patients in a Chinese Han population. A whole blood genomic DNA extraction kit was used to extract genomic DNA from the blood samples. Polymerase chain reaction restriction fragment length polymorphism was used to detect the rs402007 polymorphism of a disintegrin and metalloproteinase with thrombospondin type motifs 1 gene and the rs9619311 polymorphism of the tissue inhibitor of metalloproteinase-3 gene. The distributions of the genotypes and alleles between the 2 study groups (EH and NT) were compared. The main risk factors for EH were determined by using logistic regression analysis. The effects of gene-gene and gene-smoking interactions on EH were analyzed using multifactor dimensional reduction. RESULTS:The frequencies of the rs402007 GC?+?CC genotype and the C allele were significantly different between the EH and NT groups (0.68 vs 0.57, ??=?8.99, P?=?.003, odds ratio [OR]?=?1.19; 0.45 vs 0.32, ??=?22.16, P < .001, OR?=?1.38). The frequencies of the rs9619311 TC?+?CC genotype and the C allele were also significantly different between the 2 groups (0.33 vs 0.25, ??=?4.51, P?=?.04, OR?=?1.44; 0.18 vs 0.13, ??=?7.03, P?=?.01, OR?=?1.50). Logistic regression analysis suggests that the rs402007 and rs9619311 polymorphisms are independent risk factors for EH (OR?=?2.37, 1.86; P < .001, respectively). The multifactor dimensionality redundant analysis results showed that the interaction among rs402007, rs9619311, and smoking was statistically significant (P?=?.001). CONCLUSIONS:A disintegrin and metalloproteinase with thrombospondin type motifs 1 rs402007 and tissue inhibitor of metalloproteinase-3 rs9619311 polymorphisms are associated with EH in a Chinese Han population, and there was a positive interaction among rs402007, rs9619311, and smoking.

Dataset Information

CLPTM1L genetic polymorphisms and interaction with smoking and alcohol drinking in lung cancer risk: a case-control study in the Han population from northwest China.

Publications

CLPTM1L genetic polymorphisms and interaction with smoking and alcohol drinking in lung cancer risk: a case-control study in the Han population from northwest China.

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