Dataset Information

The Effects of Age, Cigarette Smoking, Sex, and Race on the Qualitative Characteristics of Lung Transcriptome.

ABSTRACT: The within-sample relative expression orderings (REOs) of genes, which are stable qualitative transcriptional characteristics, can provide abundant information for a disease. Methods based on REO comparisons have been proposed for identifying differentially expressed genes (DEGs) at the individual level and for detecting disease-associated genes based on one-phenotype disease data by reusing data of normal samples from other sources. Here, we evaluated the effects of common potential confounding factors, including age, cigarette smoking, sex, and race, on the REOs of gene pairs within normal lung tissues transcriptome. Our results showed that age has little effect on REOs within lung tissues. We found that about 0.23% of the significantly stable REOs of gene pairs in nonsmokers' lung tissues are reversed in smokers' lung tissues, introduced by 344 DEGs between the two groups of samples (RankCompV2, FDR <0.05), which are enriched in metabolism of xenobiotics by cytochrome P450, glutathione metabolism, and other pathways (hypergeometric test, FDR <0.05). Comparison between the normal lung tissue samples of males and females revealed fewer reversal REOs introduced by 24 DEGs between the sex groups, among which 19 DEGs are located on sex chromosomes and 5 DEGs involving in spermatogenesis and regulation of oocyte are located on autosomes. Between the normal lung tissue samples of white and black people, we identified 22 DEGs (RankCompV2, FDR <0.05) which introduced a few reversal REOs between the two races. In summary, the REO-based study should take into account the confounding factors of cigarette smoking, sex, and race.

SUBMITTER: Guan Q

PROVIDER: S-EPMC7424369 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Effects of Age, Cigarette Smoking, Sex, and Race on the Qualitative Characteristics of Lung Transcriptome.

Guan Qingzhou Q Zhang Juan J Guo You Y Xia Jie J Zhang Jiahui J Xie Jiajing J Cai Hao H Yan Haidan H Wang Xianlong X Guo Zheng Z

BioMed research international 20200804

The within-sample relative expression orderings (REOs) of genes, which are stable qualitative transcriptional characteristics, can provide abundant information for a disease. Methods based on REO comparisons have been proposed for identifying differentially expressed genes (DEGs) at the individual level and for detecting disease-associated genes based on one-phenotype disease data by reusing data of normal samples from other sources. Here, we evaluated the effects of common potential confounding ...[more]

PMID: 32802863

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Project description:ImportanceKnowing whether the effects of smoking and other risk factors with lung adenocarcinoma (ADC) incidence varies by sex would provide information on lung cancer prevention strategies.ObjectiveTo evaluate whether women in Taiwan have higher age- and tumor stage-specific lung ADC incidence rates than men irrespective of smoking status (ie, ever smoker or never smoker).Design, setting, and participantsThis population-based cohort study used data sets synthesized from the Taiwan Cancer Registry (TCR) from 1979 to 2019; the TCR Long Form (TCRLF) from 2011 to 2019, which provides individual-level smoking and tumor stage information; the Taiwan Cause of Death Database (TCOD) from 1985 to 2019; the National Health Insurance Research Database (NHIRD) from 2000 to 2020; the Monthly Bulletin of Interior Statistics (MBIS) from 2011 to 2019; the National Health Interview Survey from 2001, 2005, 2009, 2013, and 2017; and Taiwan Biobank data from 2008 to 2021. Included patients were aged 40 to 84 years and had any invasive lung cancer from January 1, 2011, to December 31, 2019.ExposureSmoking status.Main outcomes and measuresThe main outcomes were age-specific female-to-male incidence rate ratios (IRRs) of lung ADC by smoking status and tumor stage. Linked data from the TCR, TCOD, NHIRD, Taiwan National Health Interview Survey, and MBIS were used to estimate the age- and sex-specific numbers of cancer-free individuals at midyears from 2011 to 2019 by smoking status. Using the TCR and TCRLF, age-, sex-, tumor stage-, and diagnosis year-specific numbers of patients with lung ADC from 2011 to 2019 by smoking status were estimated.ResultsA total of 61 285 patients (32 599 women [53.2%]) aged 40 to 84 years (mean [SD] age, 64.66 [10.79] years) in the Taiwanese population of approximately 23 million were diagnosed with invasive lung ADC as their first lifetime cancer between 2011 and 2019. Among smokers, men had higher tobacco use by almost all examined metrics, including nearly twice the mean (SD) number of pack-years smoked (eg, 7.87 [8.30] for men aged 30-34 years vs 4.38 [5.27] for women aged 30-34 years). For 5-year age bands between 40 and 84 years, incidence of lung ADC was significantly higher among females than males for nearly all age groups irrespective of tumor stage and smoking status (eg, for the age group 70-74 years, the female-to-male IRR for late-stage lung ADC among never smokers was 1.38 [95% CI, 1.30-1.50]).Conclusions and relevanceIn this cohort study, women had higher age- and stage-specific lung ADC incidence rates than men in Taiwan for both never and ever smokers, suggesting the possibility of differential exposures between sexes to risk factors other than smoking and the potential modification of ADC risk factors by sex. Further work is needed to determine whether this pattern replicates in other populations, discover the causes of lung ADC, and put preventive measures in place.

Project description:ImportancePatterns of cigarette smoking and smoking cessation vary considerably across demographic groups in the US, but there is limited evidence on whether the hazards of smoking and benefits of quitting vary across these groups. Population-specific evidence on the benefits of quitting smoking may motivate cessation among groups historically underrepresented in medical research.ObjectiveTo quantify the association between smoking, smoking cessation, and mortality by race, ethnicity, and sex.Design, setting, and participantsThis nationally representative, prospective cohort study used data from the US National Health Interview Survey collected via questionnaire between January 1997 and December 2018 among adults aged 25 to 84 years at recruitment. Participants were followed up for cause-specific mortality through December 31, 2019.ExposuresSelf-reported smoking status at recruitment, age at quitting smoking, and years since quitting smoking.Main outcomes and measuresThe main outcomes were all-cause mortality and mortality from cancer, cardiovascular disease, and lower respiratory disease. Adjusted mortality rate ratios comparing never, former, and current smokers were calculated using Cox proportional hazards regression. Weighted analyses were conducted by race, ethnicity, and sex as reported by participants.ResultsAmong the 551 388 participants in the main analyses, the mean (SD) age at recruitment was 48.9 (15.3) years; 307 601 (55.8%) were women, 87 207 (15.8%) were Hispanic, 75 545 (13.7%) were non-Hispanic Black, 355 782 (64.5%) were non-Hispanic White, and 32 854 (6.0%) identified as other non-Hispanic race and ethnicity. There were 74 870 deaths among participants aged 25 to 89 years during follow-up (36 792 [49.1%] among men; 38 078 [50.9%] among women). The all-cause mortality rate ratio (RR) for current vs never smoking was 2.80 (95% CI, 2.73-2.88) overall. The RRs were similar by sex but varied by race and ethnicity: Hispanic, 2.01 (95% CI, 1.84-2.18); non-Hispanic Black, 2.19 (95% CI, 2.06-2.33); non-Hispanic White, 3.00 (95% CI, 2.91-3.10); and other non-Hispanic race and ethnicity, 2.16 (95% CI, 1.88-2.47). When comparing those who quit smoking before age 45 years with never smokers, all-cause mortality RRs were 1.15 (95% CI, 1.03-1.28) among Hispanic individuals, 1.16 (95% CI, 1.07-1.25) among non-Hispanic Black individuals, 1.11 (95% CI, 1.08-1.15) among non-Hispanic White individuals, and 1.17 (95% CI, 0.99-1.39) among other non-Hispanic individuals.Conclusions and relevanceIn this prospective cohort study, among men and women from diverse racial and ethnic groups, current smoking was associated with at least twice the all-cause mortality rate of never smoking. Quitting smoking, particularly at younger ages, was associated with substantial reductions in the relative excess mortality associated with continued smoking.

Dataset Information

The Effects of Age, Cigarette Smoking, Sex, and Race on the Qualitative Characteristics of Lung Transcriptome.

Publications

The Effects of Age, Cigarette Smoking, Sex, and Race on the Qualitative Characteristics of Lung Transcriptome.

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