Abstract 2756: Heavy smoking in Northeastern Ontario women is associated with polymorphisms in nicotinic acetylcholine receptor genes
Bibliographic record
Abstract
Abstract Smoking is a leading cause of premature death and is a risk factor for many serious diseases. Recent studies suggest that the nicotinic acetylcholine receptor gene region of CHRNA5-CHRNA3-CHRNB4 on chromosome 15 is associated with nicotine dependence (ND). Single nucleotide polymorphisms (SNPs) in this region may be associated with heaviness of smoking, a strong predictor of nicotine dependence. This study investigated the association of SNPs in two nicotinic acetylcholine receptor genes, CHRNA5 rs16969968 and CHRNA3 rs578776, with heaviness of smoking in primarily caucasian women in Northeastern Ontario, Canada. This study used previously collected data from a population-based case-control study designed to assess smoking and breast cancer risk in 347 women with breast cancer and 775 population-based controls using a mailed study package with questionnaire and buccal swab. The smoking phenotype, heaviness of smoking, was defined based on available self-reported questionnaire data. The 617 ever-active smoking women (who smoked at least 100 cigarettes) were refined into “heavy” or “light” smokers; heavy smokers (n=200) reported smoking 20 or more cigarettes per day (CPD) for 5 or more years; light smokers (n=71) reported smoking less than 5 CPD for one or more years. Genotyping assays and the ABI 7900 Sequence Detection System (Applied Biosystems, CA) defined SNPs. Odds Ratios (OR) and 95% Confidence Intervals (CI)s were estimated using logistic regression. Women with the homozygous variant genotype AA for CHRNA5 rs16969968 were at significantly increased risk of heavy smoking, with an age-adjusted OR of 3.2 (95% CI 1.05-10.00) in the codominant model; risks increased in a model additionally adjusted for education level and alcohol intake, with an OR of 3.9 (95% CI 1.21-12.32). Women with the homozygous variant genotype TT for CHRNA3 rs578776 were at significantly decreased risk of heavy smoking, with an age-adjusted OR of 0.33 (95% CI 0.12-0.90) and similar risk for the additionally adjusted model. The SNPs were in high linkage disequilibrium (D’ 1.0) with low correlation (r2=0.2) between the risk and protective SNPs suggesting independent associations. When assessing the combined influence of both SNPs, women with the CHRNA5 rs16969968 GG genotype and the CHRNA3 rs578776 TT genotype had the lowest risk of heavy smoking with an age-adjusted OR of 0.57 (95% CI 0.18-1.79). The AA high risk homozygous genotype for CHRNA5 rs16969968 only occurred in association with the CC genotype of CHRNA3 rs578776 and was associated with the highest risk, with an age-adjusted OR of 3.23 (0.90-11.62) and additionally adjusted OR of 3.85 (1.03-14.47). In conclusion, there was a significant positive association of the CHRNA5 rs16969968 and significant negative association of CHRNA3 rs578776 with heaviness of smoking in a population of women in Northeastern Ontario, Canada. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2756. doi:10.1158/1538-7445.AM2011-2756
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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".