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Maria Teresa Landi



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    MA06 - PDL1, TMB and DNA Repair (ID 903)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 206 AC
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      MA06.10 - Germline Mutation in ATM Affect Lung Cancer Risk with High Effect (ID 12792)

      14:35 - 14:40  |  Author(s): Maria Teresa Landi

      • Abstract
      • Presentation
      • Slides

      Background

      Genome wide association studies have identified several lung cancer susceptibility regions and common variants influencing lung cancer risk. However, few previous studies investigated the association between germline mutations and lung cancer risk.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We analyzed data from a case-control study with 19053 lung cancer cases and 15446 healthy controls of European ancestry in a discovery phase and performed a validation analysis using a case-control study comprising 4261 lung cancer cases and 4152 healthy controls of European ancestry for replication. Logistic regression was used to identify germline mutations with high effect within exome regions associated with lung cancer risk.

      4c3880bb027f159e801041b1021e88e8 Result

      We found rs56009889 in ATM was statistically associated with lung cancer risk in the discovery set (OR = 3.05, P = 3.68 × 10−8) and was nonsignificantly associated with lung cancer risk in the validation set (OR = 1.83, P = 0.16). Stratified analyses by gender with adjustment for age and smoking status showed that females carrying at least one mutated allele of rs56009889 (T/C + T/T) had an increased risk of lung cancer with ORs being 7.77 (95% CI 3.45 - 17.47) in discovery and 6.73 (95% CI 1.46–30.98) in replication, compared to C/C homozygotes among females. Individuals carrying at least one T allele showed a significant 6.9-fold increased risk for lung adenocarcinoma in discovery (adjusted OR = 6.85; 95% CI 4.37 – 10.75) and approximately a 4.9-fold increased risk in replication (adjusted OR = 4.89; 95% CI 2.01 – 11.91). Never smokers with combined genotypes (T/C + T/T) had a greater than 8-fold increased risk of lung cancer in discovery (adjusted OR = 8.03, 95% CI 4.00 – 16.13), while smokers only showed a 2.13-fold increased risk (adjusted OR = 2.13, 95% CI 1.25 – 3.65). In replication, however, the risks from this variant were comparable between smokers and nonsmokers, although the sample size is small for nonsmokers (adjusted OR = 2.16; 95% CI 0.48 – 9.79 for never-smokers and adjusted OR = 2.07; 95% CI 0.66 – 6.52 for smokers). All the T/T homozygotes of rs56009889 developed lung adenocarcinoma in discovery (P = 0.036). The association exhibited a dose-response relationship between the number of T allele of rs56009889 and lung cancer risk in discovery (Ptrend = 1.07 x 10 -9).

      8eea62084ca7e541d918e823422bd82e Conclusion

      rs56009889 highly affected the risk of lung cancer, mainly of lung adenocarcinoma, primarily in women and never smokers. These germline mutations provide important insights for the prevention of lung cancer.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MS29 - Selection into Screening Programs: Interplay of Risk Algorithms, Genetic Markers and Biomarkers (ID 807)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 206 F
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      MS29.03 - Polygenic Risk Score for Risk Assessment (ID 11527)

      14:05 - 14:20  |  Author(s): Maria Teresa Landi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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