Abstract 937: Nicotinic acetylcholine receptor polymorphisms, secondhand smoke and lung cancer risk
Bibliographic record
Abstract
Abstract Introduction: Passive or secondhand smoke (SHS) exposure is an independent risk factor for adult non-small cell lung cancer (NSCLC). In 2008, three genome wide association studies (GWAS) identified a locus on chromosome region 15q24-25.1 that was strongly associated with lung cancer. In this study, we assessed the interaction of the two most significant single nucleotide polymorphisms (SNPs) reported (rs8034191, rs1051730) with SHS on lung cancer risk. We hypothesize that after adjusting for active cigarette smoking, individuals with the risk alleles and the highest cumulative exposure to SHS are at the greatest risk of lung cancer. Methods: This study population is derived from a large ongoing case control study evaluating the molecular epidemiology of lung cancer, which began in 1992 at the Massachusetts General Hospital. The polymorphisms were genotyped by the 5V nuclease assay (Taqman) using the ABI Prism 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA). Interviewer-administered questionnaires collected information on demographics, and detailed smoking histories from each subject. Second hand smoke exposure duration and frequency was self-reported for three different activities (leisure, work and at home). The cumulative SHS exposure was the sum of all durations multiplied by their frequency weight. We used the co-dominant genetic model for individual SNPs, controlling for age, gender, pack years, years since smoking cessation and smoking status. We tested for interaction using the Likelihood Ratio Test by incorporating cross product interaction terms of indicator variables for each SNP and quartiles of cumulative exposure. Results: A total of 2071 cases and 1506 controls were analyzed. Among cases, exposure to SHS at home 1924(93%), work 1727 (83%), leisure 1791 (86%); among controls 1328 (88%), 1044 (69%) and 1233 (82%) respectively. In stratified analysis, for study participants in the highest quartile of cumulative SHS exposure and comparing the homozygous variant to the wildtype, the adjusted odds ratio (AOR) for lung cancer was 1.55 (0.99-2.44) (rs8034191) and 1.66 (1.05-2.62) (rs1051730). In the lowest quartile of SHS exposure the corresponding results were 0.94 (0.47-1.89) (rs8034191) and 0.91(0.45-1.84) (rs1051730). There was no evidence for gene-SHS interaction. Conclusion: Our results indicate that secondhand smoke does not modify the association of rs1051730 and rs8034191 with non-small cell lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 937.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.013 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".