Associations between Smoking, Opioid Analgesic Use, and Risk for Chemical Coping in Korean Patients with Advanced Cancer

Eun Hee Jung; Yu Jung Kim; Rony Dev; Koung Jin Suh; Ji-Won Kim; Se Hyun Kim; Jin Won Kim; Keun-Wook Lee; Jee Hyun Kim; Jong Seok Lee; Eduardo Bruera

doi:10.4143/crt.2025.1034

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Original Article Associations between Smoking, Opioid Analgesic Use, and Risk for Chemical Coping in Korean Patients with Advanced Cancer: Eun Hee Jung^1,2, Yu Jung Kim^1,2, Rony Dev³, Koung Jin Suh¹, Ji-Won Kim¹, Se Hyun Kim¹, Jin Won Kim¹, Keun-Wook Lee¹, Jee Hyun Kim¹, Jong Seok Lee¹, Eduardo Bruera³; DOI: https://doi.org/10.4143/crt.2025.1034
Published online: February 3, 2026

¹Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

²Center for Palliative Care and Clinical Ethics, Seoul National University Bundang Hospital, Seongnam, Korea

³Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Yu Jung Kim, Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 166 Gumi-ro, Bundang-gu, Seongnam 13620, Korea
Tel: 82-31-787-7041 E-mail: cong1005@gmail.com

• Received: September 20, 2025 • Accepted: February 2, 2026

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract

Purpose
We investigated the associations between smoking, pain expression, opioid use, substance use behaviors, coping strategies, and risk of chemical coping in Korean patients with advanced cancer.
Materials and Methods
In this prospective study, 240 patients were enrolled. Demographic and clinical information were obtained from medical records. Smoking status, symptom burden by the Edmonton Symptom Assessment System (ESAS), the Cut down/Annoyed/Guilty/Eye-opener (CAGE) alcoholism questionnaire results, morphine equivalent daily dose (MEDD), tranquilizers and coffee use, coping strategies, and physician-assessed risk of chemical coping and somatization were assessed using questionnaires and interviews.
Results
Of the 240 patients, 49 (20.4%) were current smokers, 104 (43.3%) were former smokers, and 87 (36.3%) were never-smokers. 161 were male (67.1%); 89.4% (144/161) of these men were current or former smokers, while 88.6% (70/79) of women were never-smokers (p < 0.001). ESAS pain scores did not differ by smoking status (3.0 vs. 2.9 vs. 2.7, p=0.480), but current smokers had higher MEDD (63.5 mg/day vs. 25.1 mg/day vs. 22.3 mg/day, p=0.015). Current smokers were more often CAGE-positive (32.7% vs. 16.3% vs. 2.3%, p < 0.001), heavy coffee drinkers (24.5% vs. 12.5% vs. 0%, p < 0.001) and showed a greater physician-assessed risk of chemical coping (26.5% vs. 8.7% vs. 13.8%, p=0.015).
Conclusion
Among Korean patients with advanced cancer, current smokers were more likely to use higher doses of opioids, have positive CAGE results, and drink more coffee. Close monitoring and appropriate management for the possibility of chemical coping or non-medical opioid use will be important in these patients.
Key words: Advanced cancer, Cancer pain, Opioid, Chemical coping, Smoking

Introduction

Pain control is an essential component of palliative care for patients with advanced cancer. Opioids have been a mainstay of cancer pain management, and prescribing sufficient doses of opioid analgesics to achieve adequate pain control has been emphasized for several decades. However, as the concept of chemical coping has emerged and the non-medical opioid use has become a serious problem in many countries, safe use of opioid analgesics is becoming a priority for physicians treating cancer patients [1-4].

Chemical coping has been defined heterogeneously by researchers since it was first mentioned 30 years ago [1,5-7]. In our previous studies, we defined chemical coping as the excessive or non-medical use of opioids and/or other psychotropic medications to cope with life stressors [8,9]. Kirsh et al. [5] defined chemical coping as a gray middle ground between compliant medication use and addiction. In a pilot study using the Delphi method to define chemical coping in cancer patients, the consensus definition of experts was “the use of opioids to cope with emotional distress characterized by inappropriate and/or excessive opioid use” [6,7]. Important risk factors for chemical coping include depression, psychiatric disease, substance abuse, alcoholism and smoking tobacco.

Smoking tobacco is an important factor that has close association with pain and opioid use. In the general population, tobacco smokers have been shown to report a higher prevalence of pain and more intense pain compared to nonsmokers [10,11]. Continued smoking after cancer diagnosis is reported to be associated with greater pain severity and interference from pain [12,13]. In our previous studies, a history of tobacco use was associated with increased pain expression, increased opioid dosage, and increased risk of maladaptive chemical coping in patients with advanced cancer [8,9]. Smokers were also more likely to have a history of alcoholism or illicit drug use.

Although the associations between smoking, pain expression, opioid use and the use of other potentially addictive substances are impressive, they have not yet been studied in Asian populations. In this prospective study, we aimed to examine the associations between smoking, pain expression, opioid analgesic use, substance use behaviors, coping strategies, and the risk of chemical coping in Korean patients with advanced cancer. Smoking rates among Korean adults have gradually declined, but 19.6% of adults continue to smoke tobacco as of 2023 [14].

Materials and Methods

1. Study design and subjects

This was a single-center, cross-sectional observational study conducted at Seoul National University Bundang Hospital (SNUBH) from July 2020 to March 2023. Patients aged 18 years or older who were diagnosed with advanced cancer and treated in an outpatient medical oncology clinic were enrolled. Advanced cancer, limited to solid tumors, was defined as locally advanced, metastatic, or recurrent disease. Locally advanced cancer treated with definitive chemoradiation and curative surgery was not included. Patients were eligible if they were able to communicate and provide written informed consent. The following patients were excluded: (1) those with active delirium, (2) those with significant cognitive dysfunction, (3) those with other severe medical conditions that could interfere with participation, (4) those with intellectual disabilities that would prevent them from comprehending the study, and (5) those receiving end-of-life care.

2. Data collection

We collected clinical and demographic data from electronic medical records. The demographic information included age, sex, marital status, and education level. Clinical data included the date of advanced cancer diagnosis, the primary site of the cancer, the current treatment, and the number of chemotherapy lines administered at the time of study enrollment. At the initial assessment, patients completed questionnaires, including the smoking questionnaire, the Edmonton Symptom Assessment System (ESAS) [15], the Cut down, Annoyed, Guilty, Eye-opener (CAGE) questionnaire [16], and the Brief Coping Orientation to Problems Experienced (COPE) inventory [17].

Smoking status was assessed using a questionnaire from the Behavioral Risk Factor Surveillance System (BRFSS) developed by the U.S. Centers for Disease Control and Prevention [18]. Patients were categorized into three groups: current, former, and never smokers. In accordance with the criteria used in previous studies, former smokers were defined as individuals who had smoked at least 100 cigarettes in their lifetime but were not currently smoking at the time of assessment [9]. Never smokers were defined as those who had smoked fewer than 100 cigarettes in their lifetime, while current smokers were classified as those who were actively smoking at the time of assessment. Data on the age of smoking initiation and cessation, number of cigarettes smoked per day, types of tobacco products used, and the time to first cigarette smoking after waking were obtained.

The ESAS was used to evaluate the symptom burden of the participants, including pain, fatigue, nausea, depression, anxiety, drowsiness, dyspnea, anorexia, feeling of well-being, and sleep disturbance [15]. Each symptom was measured on a numerical scale ranging from 0 (no symptoms) to 10 (worst possible symptoms). The symptom distress score was defined as the sum of the scores of nine items excluding sleep disturbance [19]. Information regarding the type and dose of analgesics and other relevant medications, including tranquilizers, was collected. Morphine equivalent daily dose (MEDD) was calculated for each patient.

The CAGE questionnaire is a validated tool for screening for alcohol use disorder [16]. The questionnaire consists of 4 items, with each affirmative response scored as one point. The total score ranges from 0 to 4, and a score of ≥ 2 is considered indicative of a potential for alcohol use disorder. Since most other substances that could potentially cause habitual use or dependence are not available and are strictly prohibited in Korea, we added the use of coffee to the survey as an exploratory endpoint. A person who drinks three or more cups of coffee every day was considered a heavy coffee drinker in this study. The Brief COPE inventory is an assessment tool of coping strategies for specific stressors [17]. Twenty-eight items are divided into 14 subscales of two items each, measuring the different coping styles. Each item is rated on a 4-point scale ranging from 1 (I have not been doing this at all) to 4 (I have been doing this a lot), with higher scores indicating greater use of the corresponding coping strategy.

In addition, palliative care physicians and medical oncologists with palliative care experience were asked to determine whether the patient was at risk for chemical coping and somatization based on patient interview, behavior, and medical history. Chemical coping was defined as excessive or non-medical use of opioids and/or other psychotropic medications to cope with life stressors [9], and somatization was defined as a syndrome of unexplained physical symptoms that are distressing and may be caused or exacerbated by emotional distress [20]. Physicians were unaware of the patient’s questionnaire results at the time of assessment.

3. Statistical analysis

Descriptive analysis was performed for all patients. We compared patient characteristics and outcomes according to smoking status. To compare the differences between groups, the chi-square test (or Fisher’s exact test when cell counts were small) was used for categorical variables, and analysis of variance (ANOVA) or the Kruskal-Wallis test was used for continuous variables. If the overall p-value was significant among the three groups, post hoc pairwise comparisons were conducted to explore differences between two groups. Spearman’s rank correlation was used to examine the association between the duration of opioid use and MEDD. To identify independent predictors of MEDD, a hierarchical multiple regression analysis was performed, adjusting for potential clinical variables. All the statistics were two-sided, and statistical significance was defined as a p-value < 0.05. All data were analyzed using IBM SPSS Statistics for Windows ver. 25.0 (IBM Corp.).

4. Sample size justification

Assuming that 60% of patients with advanced cancer were either current or former smokers, with each group comprising approximately 30%, the prevalence of maladaptive chemical coping was expected to be 25% among those with a smoking history and 10% among never smokers. We determined the sample size to be 213 patients via a two-proportion Z test with pooled variance, which is consistent with our assumptions. A total of 240 patients were planned for enrollment, allowing for potential dropout and incomplete data. A two-sided Fisher’s exact test, conducted with a 5% type I error rate, demonstrated 89% power to detect a 15% difference (10% vs. 25%) between current smokers and never smokers and 96% power to detect a difference between former smokers and never smokers.

Results

Among the 240 patients, 49 (20.4%) were current smokers, 104 (43.3%) were former smokers, and 87 (36.3%) were never smokers. The median age of the patients was 64 years (range, 24 to 88 years), with no difference according to smoking status. Two-thirds (n=161, 67.1%) of the patients were male, 89.4% (144/161) of the male patients were current or former smokers, while 88.6% (70/79) of the female patients were never smokers (p < 0.001). There was no significant difference in the history of underlying psychiatric diseases according to smoking status (p=0.468). Thoracic cancer (59.6%) was the most common primary type for patients, and 87.1% of patients were receiving palliative chemotherapy. The median number of previous lines of chemotherapy was lower among current or former smokers than among never smokers. There was no significant difference in the ESAS symptom burden according to smoking status. The baseline characteristics of the patients by smoking status are summarized in Table 1.

The mean pain score measured by the ESAS was numerically slightly higher in the current and former smoker groups, but there was no significant difference according to smoking status (3.0 vs. 2.9 vs. 2.7, p=0.480). However, the mean MEDD differed significantly among the groups (Table 2). It was highest, at 63.5 mg/day, in current smokers, 25.1 mg/day in former smokers, and 22.3 mg/day in never smokers (p=0.015). To control for potential confounding factors, a hierarchical multiple regression analysis was performed. After adjusting for clinically and statistically relevant confounders—sex, line of chemotherapy, presence of neuropathic pain, duration of opioid use, and ESAS pain score, current smoking remained a significant independent predictor of higher MEDD (β=–0.292, p=0.037) (Table 3). Furthermore, the duration of opioid use showed no significant correlation with MEDD (Spearman’s ρ=–0.130, p=0.207). The proportions of patients with a MEDD ≥ 30 mg/day (42.9% vs. 23.1% vs. 18.4%, p=0.065) and ≥ 120 mg/day (12.2% vs. 7.7% vs. 6.9%, p=0.567) were numerically greater among current smokers.

Overall, 35 patients (14.6%) were CAGE-positive (Table 4), and current smokers were more likely to screen positive than were former or never smokers (32.7% vs. 16.3% vs. 2.3%, p < 0.001). There were no significant differences in the prevalence of underlying liver disease (13/240, 5.4%; p > 0.99) or liver metastases (34/240, 14.2%; p=0.631) between the three groups, indicating that these associations remained consistent regardless of liver-related factors. Among 21.7% (52/240) of patients who were taking tranquilizers prescribed by physicians, 15 patients took them to relieve stress, with no difference according to smoking status. More than three-quarters of the patients (77.5%) were coffee drinkers, and 25 patients (10.4%) drank three or more cups of coffee every day. Current or former smokers were more likely to drink coffee (83.7% vs. 86.5% vs. 63.2%, p < 0.001), to be heavy coffee drinkers (24.5% vs. 12.5% vs. 0%, p < 0.001), and to drink coffee to relieve stress (22.4% vs. 18.3% vs. 6.9%, p=0.008). According to the Brief COPE questionnaire, maladaptive coping strategies were not found to be more prevalent among patients with a history of smoking (S1 Table).

Physician-assessed risk of chemical coping was highest in current smokers (26.5% vs. 8.7% vs. 13.8%, p=0.015) (Table 5). However, most probable/confirmed cases of chemical coping or somatization were found in the never smoker group. There were no significant differences among groups in terms of the risk of somatization.

Discussion

In this prospective study of patients with advanced cancer treated at an outpatient medical oncology clinic of a large comprehensive cancer center in Korea, the MEDD of current smokers was significantly greater than that of former smokers or never smokers. In addition, current smokers were more likely to screen positive on the CAGE questionnaire and to be heavy coffee drinkers. The physician-assessed risk of chemical coping was significantly higher in current smokers.

Unlike in a similarly conducted U.S. study [9], in this study, the median age was not younger, and the education level was not lower among current smokers. Interestingly, 98% of current smokers were male in this study, while approximately half of the current smokers were female in the U.S. study. This finding may have contributed to the lack of significant differences in pain expression between smokers and nonsmokers in the current study. Previous studies have reported that women generally have higher pain sensitivity and higher pain intensity than men [21]. Additionally, in the present study, nearly 90% of patients were receiving active chemotherapy, and many of them were receiving first- or second-line chemotherapy. Thus, the overall symptom burden was not very high, and the mean ESAS score for pain was only 2.9. Despite significant differences in baseline patient characteristics, it is notable that current smokers in both studies required higher doses of opioids in terms of the MEDD, were more likely to screen positive on the CAGE questionnaire and were more likely to be assessed by physicians as being at risk for chemical coping.

Although the mean ESAS pain scores were generally low in the overall population and there were no significant differences in terms of pain expression among the groups, current smokers had a significantly greater MEDD than former or never smokers. Interestingly, our analysis demonstrated that current smokers required higher doses of opioids despite a shorter duration of use compared to never smokers. This paradoxical finding was supported by our hierarchical regression analysis, which showed that smoking status maintained a significant association with higher MEDD even after adjusting for clinical covariates. These findings suggest that increased opioid use among current smokers is not solely attributable to increased pain severity or the cumulative effect of prolonged treatment but may reflect complex biopsychosocial mechanisms in this patient group. Polycyclic aromatic hydrocarbons in smoke induce hepatic microsome enzymes. This enzyme induction accelerates opioid metabolism and reduces the bioavailability of some opioids, such as methadone and hydrocodone, resulting in lower serum concentrations and analgesic efficacy [22,23]. Additionally, chronic nicotine exposure can affect the endogenous pain modulation pathways and influence opioid tolerance [24,25]. Psychologically, previous studies have demonstrated that smokers are more likely to use maladaptive coping strategies, such as using substances for emotional relief and coping with stress [9,26]. Moreover, nicotine withdrawal is associated with increased pain sensitivity, which might promote opioid use [27]. Taniguchi et al. [28] reported that cancer patients who continued to smoke after diagnosis were significantly more likely to require strong opioids than patients who quit smoking despite having similar clinical characteristics. As such, careful assessment of chemical coping risks and individualized approaches to pain and opioid prescription might be important for patients with advanced cancer who smoke to obtain effective analgesia while minimizing opioid-related harm.

In Korea, the use of illegal drugs is strictly prohibited, and many people have antipathy even toward the medical use of opioids and psychotropic drugs. Therefore, we could not use the same questionnaires used in the U.S. study to assess patients’ risk for illegal substance use. Meanwhile, Korea is a country with very high annual alcohol and coffee consumption. To assess the association between smoking and the potential risk of non-medical opioid use, we analyzed the use of alcohol, prescribed tranquilizers, and coffee in this study. As expected, current smokers were more likely to be CAGE-positive compared to former smokers or never smokers (32.7% vs. 16.3% vs. 2.3%, p < 0.001). Interestingly, current smokers or former smokers were more likely to drink coffee compared to never smokers and were significantly more likely to be heavy coffee drinkers (24.5% vs. 12.5% vs. 0%, p < 0.001). To the best of our knowledge, our study is the first study to show an association between smoking and coffee consumption in patients with advanced cancer.

Interestingly, former smokers consistently revealed intermediate patterns across multiple domains—including opioid use, substance-related coping behaviors, and adaptive coping strategies—that were positioned between those of current and never smokers. Although these patients did not actively smoke, their residual behaviors suggest that prior smoking may have lasting effects on pain perception, coping mechanisms, or neurobiological sensitivity to distress. These findings are consistent with previous reports indicating that the use of opioids and other substances, coping behaviors, and stress responses of former smokers differ from those of never smokers, even after smoking cessation [29,30]. Thus, rather than focusing solely on current smoking status, reviewing the overall smoking history may be important. Early screening and intervention for former smokers might help reduce the risk of maladaptive opioid chemical coping and improve symptom management during the treatment of advanced cancer.

The physician-assessed risk of chemical coping was significantly higher among current smokers, but never smokers also had a considerable risk of chemical coping. Notably, four of the five patients assessed by physicians as having probable/confirmed chemical coping were female never smokers with high levels of emotional distress (data not shown). All four of these patients were assessed to have a risk for somatization, and two of the four patients were assessed as having probable/confirmed somatization. Risks for chemical coping may include patients ranging from current smokers who require higher doses of opioid analgesics and frequently use other potentially addictive substances such as alcohol or coffee to female never smokers with high levels of emotional distress and somatization. We cautiously speculate that these two characteristic groups may overlap depending on smoking prevalence among women.

This study has several limitations. First, most patients did not experience significant pain and many did not use opioids. This may lead to difficulties in interpreting the association between smoking, pain expression and opioid use. Our study was a single-center study, and the generalizability of our findings to other populations may be limited. To clarify these associations, future research should be conducted in multi-center designs with larger sample sizes. Second, much of the data, including pain scores, opioid use, substance use behaviors, and coping strategies, are based on self-reported scores, which may be subject to social desirability bias and underreporting. Specifically, while the CAGE questionnaire is an efficient screening tool for alcohol use disorder, it has limitations in assessing the detailed severity of dependence; thus, additional use of more comprehensive instruments might be considered in future research. Third, while we discussed the potential influence of hepatic enzyme induction and nicotine exposure on opioid metabolism, our study did not include genetic analysis. Future pharmacogenetic studies focusing on the liver enzyme system in Asian populations and biospecimen collections would provide a better understanding of the neurobiological mechanisms underlying these associations. Despite these limitations, our results provide valuable insight into the behavioral, racial/ethnic, and social factors that may influence the risk of maladaptive chemical coping in patients with advanced cancer.

Our study found that current smokers among Korean patients with advanced cancer were more likely to have a positive CAGE score, require higher doses of opioid analgesics and were more likely to use potentially addictive substances such as alcohol or coffee. Early and proactive identification of risk for maladaptive chemical coping and integration of behavioral support into symptom management will be necessary in these populations. Future longitudinal and multicenter studies are needed to further explore the nature of chemical coping and to develop appropriate interventions for high-risk patients.

Electronic Supplementary Material

Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).

crt-2025-1034_S1_Table.pdf

NOTES

Ethical Statements

The Institutional Review Board of SNUBH approved this study (B-2006-618-308), which was conducted in accordance with the Declaration of Helsinki and written informed consent was obtained from all patients.

Author Contributions

Conceived and designed the analysis: Kim YJ, Dev R, Bruera E.

Collected the data: Jung EH, Kim YJ, Suh KJ, Kim JW (Ji-Won Kim), Kim SH, Kim JW (Jin Won Kim), Lee KW, Kim JH, Lee JS.

Performed the analysis: Jung EH.

Wrote the paper: Jung EH, Kim YJ (with revisions from all authors).

Approved the final version: all authors.

Conflicts of Interest

Conflict of interest relevant to this article was not reported.

Funding

This work was supported by a grant from Seoul National University Bundang Hospital (grant number 02-2015-0025). The sponsor had no influence on the study design, data acquisition, analysis, interpretation, or writing of this manuscript.

Acknowledgments

The results of this study have been submitted to the Korean Society for Medical Oncology Congress 2023 and the 15th Asia Pacific Hospice Palliative Care Conference.

Table 1.

Baseline patients’ characteristics and symptom burden according to smoking status

Characteristic	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
Age (yr)	64 (24-88)	62 (38-81)	67 (41-87)	64 (24-88)	0.484
Sex					< 0.001
Male	161 (67.1)	48 (98.0)	96 (92.3)	17 (19.5)
Female	79 (32.9)	1 (2.0)	8 (7.7)	70 (80.5)
Marital status					0.184
Married	186 (77.5)	35 (71.4)	88 (84.6)	63 (72.4)
Not married	11 (4.6)	5 (10.2)	2 (1.9)	4 (4.6)
Divorced/Bereaved	43 (17.9)	9 (18.4)	14 (13.5)	20 (23.0)
Education					0.667
College or advanced degree	77 (32.1)	18 (36.7)	33 (31.7)	26 (29.9)
High school or less	163 (67.9)	31 (63.3)	71 (68.3)	61 (70.1)
History of underlying psychiatric disease	41 (17.1)	11 (22.4)	15 (14.4)	15 (17.2)	0.468
Cancer type					0.172
Thoracic	143 (59.6)	28 (57.1)	65 (62.5)	50 (57.5)
Gastrointestinal	13 (5.4)	6 (12.2)	5 (4.8)	2 (2.3)
Genitourinary	39 (16.3)	8 (16.3)	22 (21.2)	9 (10.3)
Breast	7 (2.9)	0	1 (1.0)	6 (6.9)
Others	38 (15.8)	7 (14.3)	11 (10.6)	20 (23.0)
Current treatment					0.840
Palliative chemotherapy	209 (87.1)	43 (87.8)	91 (87.5)	75 (86.2)
Supportive care only	31 (12.9)	6 (12.2)	13 (12.5)	12 (13.8)
Previous lines of chemotherapy at enrollment					0.003
0	2 (0.8)	0	2 (1.9)	0
1	103 (42.9)	30 (61.2)	45 (43.3)	28 (32.2)
2	73 (30.4)	14 (28.6)	30 (28.8)	29 (33.3)
3	62 (25.8)	5 (10.2)	27 (26.0)	30 (34.5)
ESAS
Pain	2.9±2.9	3.0±2.7	2.9±2.9	2.7±2.9	0.480
Fatigue	3.9±2.6	4.0±2.1	4.1±2.7	3.5±2.7	0.158
Nausea	0.8±1.7	1.0±1.5	0.8±1.8	0.8±1.6	0.274
Depression	2.2±2.6	2.4±2.7	2.3±2.7	1.9±2.4	0.593
Anxiety	1.9±2.6	2.2±2.8	1.8±2.6	1.9±2.4	0.486
Drowsiness	2.8±2.6	3.2±2.7	3.0±2.7	2.5±2.6	0.208
Dyspnea	2.4±2.6	2.5±2.7	2.7±2.8	2.0±2.4	0.332
Anorexia	3.7±3.0	4.1±3.3	3.5±3.0	3.6±2.8	0.607
Feeling of well-being	4.0±2.5	4.2±2.5	4.1±2.4	3.8±2.5	0.545
Sleep disturbance	2.7±2.8	2.8±2.8	2.6±2.8	2.7±2.8	0.926
Symptom distress score	24.5±15.2	26.6±14.4	25.1±15.9	22.6±14.6	0.296
Neuropathic pain	18 (7.5)	3 (6.1)	9 (8.7)	6 (6.9)	0.856

Value are presented as median (range), number (%), or mean±standard deviation. ESAS, Edmonton Symptom Assessment System.

Table 2.

ESAS pain score and opioid use according to smoking status

Characteristic	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
ESAS pain score	2.9±2.9	3.0±2.7	2.9±2.9	2.7±2.9	0.480
MEDD (mg), mean (range)	31.9 (0-960)	63.5 (0-960)	25.1 (0-252)	22.3 (0-358)	0.015
Patients with a MEDD ≥ 30 mg/day	61 (25.4)	21 (42.9)	24 (23.1)	16 (18.4)	0.065
Patients with a MEDD ≥ 120 mg/day	20 (8.3)	6 (12.2)	8 (7.7)	6 (6.9)	0.567
Duration of opioid use (day), median (range)	221 (0-2,746)	109 (5-842)^a)	298 (50-1,758)^b)	350 (0-2,746)^b)	0.013

Value are presented as mean±standard deviation or number (%) unless otherwise indicated. ESAS, Edmonton Symptom Assessment System; MEDD, Morphine equivalent daily dose.

^a),b) Different superscripts indicate significant differences between groups (p < 0.05) by Bonferroni-adjusted pairwise comparisons.

Table 3.

Hierarchical multiple regression analysis for factors associated with MEDD

Variable	Model 1			Model 2
Variable	B	β	p-value	B	β	p-value
Constant	–17.455		0.767	–6.642		0.909
Sex (male vs. female)	–18.255	–0.069	0.516	32.097	0.121	0.379
Line of chemotherapy	43.228	0.178	0.086	50.082	0.207	0.045
Neuropathic pain (yes vs. no)	–31.716	–0.110	0.298	–28.728	–0.099	0.337
Duration of opioid use	< 0.001	0.000	1.000	0.007	0.030	0.778
ESAS pain score	7.212	0.183	0.086	7.567	0.192	0.066
Smoking status	-	-	-	–42.804	–0.292	0.037
R²	-	0.080	-	-	0.125	-
Adjusted R²	-	0.030	-	-	0.066	-
F (p-value)	-	1.581 (0.174)	-	-	2.118 (0.059)	-

Variance Inflation Factor of all variables was < 2.0. B, unstandardized coefficient; β, standardized coefficient; ESAS, Edmonton Symptom Assessment System; F, F-statistic; MEDD, Morphine equivalent daily dose; R², coefficient of determination.

Table 4.

Risk of non-medical drug use and potentially addictive substance use according to smoking status

Characteristic	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
Patients with CAGE positive (≥ 2)	35 (14.6)	16 (32.7)	17 (16.3)	2 (2.3)	< 0.001
Patients taking tranquilizers	52 (21.7)	13 (26.5)	23 (22.1)	16 (18.4)	0.416
To relieve stress	15 (6.2)	3 (6.1)	6 (5.8)	6 (6.8)	0.785
Coffee drinker	186 (77.5)	41 (83.7)	90 (86.5)	55 (63.2)	< 0.001
Heavy coffee drinker (≥ 3 cups/day)	25 (10.4)	12 (24.5)	13 (12.5)	0	< 0.001
To relieve stress	36 (15.0)	11 (22.4)	19 (18.3)	6 (6.9)	0.008

Values are presented as number (%). CAGE, Cut down/Annoyed/Guilty/Eye-opener.

Table 5.

Physician assessed risk of chemical coping and somatization according to smoking status

Palliative care physician assessment	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
Chemical coping					0.015
No evidence	206 (85.8)	36 (73.5)	95 (91.3)	75 (86.2)
Possible at risk	29 (12.1)	13 (26.5)	8 (7.7)	8 (9.2)
Probable/Confirmed	5 (2.1)	0	1 (1.0)	4 (4.6)
Somatization					0.181
No evidence	201 (83.8)	42 (85.7)	91 (87.5)	68 (78.2)
Possible at risk	37 (15.4)	7 (14.3)	13 (12.5)	17 (19.5)
Probable/Confirmed	2 (0.8)	0	0	2 (2.3)

Values are presented as number (%).

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Associations between Smoking, Opioid Analgesic Use, and Risk for Chemical Coping in Korean Patients with Advanced Cancer

DOI: https://doi.org/10.4143/crt.2025.1034

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Abstract
Introduction
Materials and Methods
Results
Discussion
Electronic Supplementary Material
NOTES
REFERENCES

Associations between Smoking, Opioid Analgesic Use, and Risk for Chemical Coping in Korean Patients with Advanced Cancer

Characteristic	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
Age (yr)	64 (24-88)	62 (38-81)	67 (41-87)	64 (24-88)	0.484
Sex					< 0.001
Male	161 (67.1)	48 (98.0)	96 (92.3)	17 (19.5)
Female	79 (32.9)	1 (2.0)	8 (7.7)	70 (80.5)
Marital status					0.184
Married	186 (77.5)	35 (71.4)	88 (84.6)	63 (72.4)
Not married	11 (4.6)	5 (10.2)	2 (1.9)	4 (4.6)
Divorced/Bereaved	43 (17.9)	9 (18.4)	14 (13.5)	20 (23.0)
Education					0.667
College or advanced degree	77 (32.1)	18 (36.7)	33 (31.7)	26 (29.9)
High school or less	163 (67.9)	31 (63.3)	71 (68.3)	61 (70.1)
History of underlying psychiatric disease	41 (17.1)	11 (22.4)	15 (14.4)	15 (17.2)	0.468
Cancer type					0.172
Thoracic	143 (59.6)	28 (57.1)	65 (62.5)	50 (57.5)
Gastrointestinal	13 (5.4)	6 (12.2)	5 (4.8)	2 (2.3)
Genitourinary	39 (16.3)	8 (16.3)	22 (21.2)	9 (10.3)
Breast	7 (2.9)	0	1 (1.0)	6 (6.9)
Others	38 (15.8)	7 (14.3)	11 (10.6)	20 (23.0)
Current treatment					0.840
Palliative chemotherapy	209 (87.1)	43 (87.8)	91 (87.5)	75 (86.2)
Supportive care only	31 (12.9)	6 (12.2)	13 (12.5)	12 (13.8)
Previous lines of chemotherapy at enrollment					0.003
0	2 (0.8)	0	2 (1.9)	0
1	103 (42.9)	30 (61.2)	45 (43.3)	28 (32.2)
2	73 (30.4)	14 (28.6)	30 (28.8)	29 (33.3)
3	62 (25.8)	5 (10.2)	27 (26.0)	30 (34.5)
ESAS
Pain	2.9±2.9	3.0±2.7	2.9±2.9	2.7±2.9	0.480
Fatigue	3.9±2.6	4.0±2.1	4.1±2.7	3.5±2.7	0.158
Nausea	0.8±1.7	1.0±1.5	0.8±1.8	0.8±1.6	0.274
Depression	2.2±2.6	2.4±2.7	2.3±2.7	1.9±2.4	0.593
Anxiety	1.9±2.6	2.2±2.8	1.8±2.6	1.9±2.4	0.486
Drowsiness	2.8±2.6	3.2±2.7	3.0±2.7	2.5±2.6	0.208
Dyspnea	2.4±2.6	2.5±2.7	2.7±2.8	2.0±2.4	0.332
Anorexia	3.7±3.0	4.1±3.3	3.5±3.0	3.6±2.8	0.607
Feeling of well-being	4.0±2.5	4.2±2.5	4.1±2.4	3.8±2.5	0.545
Sleep disturbance	2.7±2.8	2.8±2.8	2.6±2.8	2.7±2.8	0.926
Symptom distress score	24.5±15.2	26.6±14.4	25.1±15.9	22.6±14.6	0.296
Neuropathic pain	18 (7.5)	3 (6.1)	9 (8.7)	6 (6.9)	0.856

Characteristic	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
ESAS pain score	2.9±2.9	3.0±2.7	2.9±2.9	2.7±2.9	0.480
MEDD (mg), mean (range)	31.9 (0-960)	63.5 (0-960)	25.1 (0-252)	22.3 (0-358)	0.015
Patients with a MEDD ≥ 30 mg/day	61 (25.4)	21 (42.9)	24 (23.1)	16 (18.4)	0.065
Patients with a MEDD ≥ 120 mg/day	20 (8.3)	6 (12.2)	8 (7.7)	6 (6.9)	0.567
Duration of opioid use (day), median (range)	221 (0-2,746)	109 (5-842)^a)	298 (50-1,758)^b)	350 (0-2,746)^b)	0.013

Variable	Model 1			Model 2
Variable	B	β	p-value	B	β	p-value
Constant	–17.455		0.767	–6.642		0.909
Sex (male vs. female)	–18.255	–0.069	0.516	32.097	0.121	0.379
Line of chemotherapy	43.228	0.178	0.086	50.082	0.207	0.045
Neuropathic pain (yes vs. no)	–31.716	–0.110	0.298	–28.728	–0.099	0.337
Duration of opioid use	< 0.001	0.000	1.000	0.007	0.030	0.778
ESAS pain score	7.212	0.183	0.086	7.567	0.192	0.066
Smoking status	-	-	-	–42.804	–0.292	0.037
R²	-	0.080	-	-	0.125	-
Adjusted R²	-	0.030	-	-	0.066	-
F (p-value)	-	1.581 (0.174)	-	-	2.118 (0.059)	-

Characteristic	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
Patients with CAGE positive (≥ 2)	35 (14.6)	16 (32.7)	17 (16.3)	2 (2.3)	< 0.001
Patients taking tranquilizers	52 (21.7)	13 (26.5)	23 (22.1)	16 (18.4)	0.416
To relieve stress	15 (6.2)	3 (6.1)	6 (5.8)	6 (6.8)	0.785
Coffee drinker	186 (77.5)	41 (83.7)	90 (86.5)	55 (63.2)	< 0.001
Heavy coffee drinker (≥ 3 cups/day)	25 (10.4)	12 (24.5)	13 (12.5)	0	< 0.001
To relieve stress	36 (15.0)	11 (22.4)	19 (18.3)	6 (6.9)	0.008

Palliative care physician assessment	Total (n=240)	Current smoker (n=49)	Former smoker (n=104)	Never smoker (n=87)	p-value
Chemical coping					0.015
No evidence	206 (85.8)	36 (73.5)	95 (91.3)	75 (86.2)
Possible at risk	29 (12.1)	13 (26.5)	8 (7.7)	8 (9.2)
Probable/Confirmed	5 (2.1)	0	1 (1.0)	4 (4.6)
Somatization					0.181
No evidence	201 (83.8)	42 (85.7)	91 (87.5)	68 (78.2)
Possible at risk	37 (15.4)	7 (14.3)	13 (12.5)	17 (19.5)
Probable/Confirmed	2 (0.8)	0	0	2 (2.3)

Table 1. Baseline patients’ characteristics and symptom burden according to smoking status

Value are presented as median (range), number (%), or mean±standard deviation. ESAS, Edmonton Symptom Assessment System.

Table 2. ESAS pain score and opioid use according to smoking status

Value are presented as mean±standard deviation or number (%) unless otherwise indicated. ESAS, Edmonton Symptom Assessment System; MEDD, Morphine equivalent daily dose.

a),b)

Different superscripts indicate significant differences between groups (p < 0.05) by Bonferroni-adjusted pairwise comparisons.

Table 3. Hierarchical multiple regression analysis for factors associated with MEDD

Table 4. Risk of non-medical drug use and potentially addictive substance use according to smoking status

Values are presented as number (%). CAGE, Cut down/Annoyed/Guilty/Eye-opener.

Table 5. Physician assessed risk of chemical coping and somatization according to smoking status