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American Journal of Cancer Research logoLink to American Journal of Cancer Research
. 2019 Nov 1;9(11):2493–2514.

Post-diagnosis smoking and risk of cardiovascular, cancer, and all-cause mortality in survivors of 10 adult cancers: a prospective cohort study

Yafeng Wang 1,*, Huan Tao 2,*, Raheem J Paxton 3, Junfeng Wang 4, Sumaira Mubarik 1, Yongqian Jia 2, Wei Wang 5, Chuanhua Yu 1,6
PMCID: PMC6895457  PMID: 31815049

Abstract

Several studies have examined the relationship between smoking and mortality in cancer survivors. However, few have reported the relationships in several cancer sites (i.e., bladder, non-melanoma skin, uterine, melanoma, and lymphoma), and limited data exist on the dose-response relationship between number of cigarettes smoked per day or duration of smoking cessation and mortality. Cancer survivors (N = 35,093, 61% female, mean age = 47 years old) from the National Health Interview Survey with linked data retrieved from the National Death Index served as our study participants. Cox proportional-hazards models were used to assess associations between smoking status, all-cause, and disease-specific mortality. After a median follow-up of 13 years, 11,066 deaths occurred. Survivors who reported smoking at study entry had a 73%, 75%, 85% higher risk for cardiovascular disease, cancer, and all-cause mortality, respectively when compared to nonsmokers. Former smokers had a 31% and 37% higher risk of all-cause and cancer mortality, respectively when compared to nonsmokers. The observed relationships appeared to differ by the number of cigarettes smoked (i.e., ≥ 10 per day), especially for breast, cervix, lung, prostate, uterine and non-melanoma skin cancer survivors. Those who continued smoking post diagnosis were at greatest risk of all-cause and cancer mortality, but the associations varied substantially by cancer site. These data provide sufficient evidence of the health hazards associated with smoking for cancer survivors and provide further support for public health strategies designed to curb smoking in this vulnerable population.

Keywords: Post-diagnosis smoking, all-cause, cardiovascular, cancer survivors, mortality, cohort

Introduction

The number of cancer survivors is expected to reach 19 million by 2024 in the United States [1]. Cancer survivors represent a vulnerable population because they have a higher risk for cardiovascular disease (CVD), diabetes, osteoporosis, second cancers, and premature mortality when compared to age-matched controls [2-4]. Given their increased vulnerability to chronic health conditions, the American Cancer Society and the Institute of Medicine has advocated for engaging in healthy lifestyle behaviors throughout the survivorship continuum [5,6]. Smoking, in particular, may increase one’s risk for cancer because it stimulates cancer-promoting signaling cascades [7-9]. However, for those with a prior cancer diagnosis, it may escalate the risk for poor cancer-specific and all-cause mortality [10]. Thus, it is of considerable importance to clarify the association between smoking and risk of disease-specific and all-cause mortality among cancer survivors who smoke.

Previous studies have examined the association between smoking and disease-specific mortality among cancer survivors [11-18]. The studies in their entirety have confirmed associations between smoking and all-cause mortality among colon, prostate, and lung cancer survivors [13,14,19,20], and for cancer-specific mortality among colon, prostate, and breast cancer survivors [13,14,19,21,22]. However, several gaps in the literature remain unknown. For example, to our knowledge, few if any studies have examined the relationship between smoking and mortality in bladder, lymphoma, and uterine cancer survivors. In addition, limited data exist on the dose-response relationship between number of cigarettes smoked per day or duration of smoking cessation and mortality [14].

Therefore, the purpose of this study was to examine the relationship between both post-diagnosis smoking status and smoking intensity and both all-cause and disease-specific mortality among cancer survivors in the United States.

Materials and methods

Study population

The National Health Interview Survey (NHIS) is a stratified, multistage probability survey designed to examine the prevalence and incidence of disease and disability as well as the use of health care services in the United States. Black and Hispanic were oversampled to ensure equal representation in the study, but sample weights were used to ensure that estimates conform to national ethnic proportions. A detailed description of the probability sampling strategy and consenting methods were described elsewhere [23].

A total of 35,093 cancer adults from the 13 cross-sectional waves identified from 1997 to 2013 and their linked mortality data ending on December 31, 2015 were included in this analysis. For site-specific cancer, we focused on the ten most common cancer sites (i.e., bladder, breast, cervix, colon, lung, prostate, non-melanoma skin, uterine, melanoma, and lymphoma).

Mortality

Ascertainment of mortality was established using the International Classification of Diseases-10 Revision codes [24]. Study outcomes were defined as follows: 1) all-cause mortality; 2) cancer mortality (C00 to C97); and 3) CVD-mortality (I00 to I09, I11, I13, and I20 to I51, I60 to I69).

Exposure assessment

Smoking status (never, former, or current) was ascertained at the initial interview via two binary coded (i.e., yes/no) items: 1) have you smoked at least 100 cigarettes in your entire life? and 2) do you now still smoke cigarettes? Those participants responding “No” to both questions were classified as nonsmokers. Those participants responding “Yes” to the first item and “No” the second item were classified as former smokers). Those who responded “Yes” to both questions were classified as current smokers. To distinguish between current and former smokers, time since last cigarette (i.e., quit ≥ 20 years ago; quit 10 to 19 years ago; quit < 10 years ago) were used to classify former smokers, and cigarettes smoked per day (i.e. > 10 cigarettes per day; ≤ 10 cigarettes per day) were used to classify current smoker.

Covariates

Several covariates were included in the study. In particular, we included demographic variables (i.e., race, gender, education, and marital status), lifestyle variables (i.e., body mass index, physical activity, and alcohol consumption), comorbid conditions (i.e., hypertension, stroke and coronary heart disease), and self-rated health. Body mass index was calculated as weight in kilograms divided by height in meters squared.

Detailed information on the highest level of school completed was collected and the variable was categorized as “less than high school degree” (high school not completed), “high school degree” (high school diploma or general equivalency diploma), and “more than high school degree” (some college, vocational, or technical school; associate’s degree; Bachelor’s, Master’s, or professional degree) [25].

NHIS study participants answered questionnaires about their alcohol consumption and patterns of use [26]. These questions obtained information about the following: 1) consumption of ≥ 12 drinks in one’s lifetime, in any previous year, or the past year; 2) drinking frequency (days per week, month, or year) and drinking quantity (drinks per day) in the past year; and 3) binge drinking in the past year. Using these variables, we categorized survivors into four alcohol consumption groups: 1) lifetime abstainers: < 12 drinks in one’s lifetime; 2) former drinkers: ≥ 12 drinks in a previous year; 3) current drinker: current use of drinks/week.

Socioeconomic status was assessed based on the family income to poverty ratio (PIR) [27]. We separated participants into 3 groups: low-income (i.e., at or below the poverty ratio), middle-income (i.e., above the PIR to < 4), and high-income (i.e., PIR, ≥ 4) adults.

Statistical analysis

Weighted descriptive characteristics were used to describe the sample. Chi-square test of independence was used to examine categorical differences in the weighted percentages by smoking status. We also used Cox proportional hazard models with proportionality assumptions to examine all associations between smoking status and disease-specific and all-cause mortality. We adjusted for potential covariates and conducted two sensitivity analyses: (1) exclusion of individuals who died within the first 2-years and (2) participants with a history of CHD or stroke. In addition, we made comparisons between current smokers (> 10 cigarettes per day; ≤ 10 cigarettes per day) and former smokers (quit ≥ 20 years ago; quit 10 to 19 years ago; quit < 10 years ago). All analyses took into account the complex survey design (strata, clusters, and weights). All analyses were performed using STATA version 13.0 (Stata Corp, College Station, TX, USA). All P-values were two-sided and statistical significance was determined at P ≤ 0.05.

Results

The mean age of participants was 47 years at study entry. Compared with nonsmokers, former or current smokers were more likely to be men and non-Hispanic whites (p-value < 0.001). Never smokers appeared to be more educated. Current smokers were less physically active, leaner (i.e., BMI < 25 kg/m2) and consumed more alcohol. Former smokers were more likely to have a history of hypertension, diabetes, CHD and stroke. Descriptive statistics were reported in Table 1.

Table 1.

Baseline characteristics of cancer patients by smoking status

Characteristic Subgroups Never smoking Former smoking Current smoking P value
No. % No % No %
Age < 0.001
< 45 years 2364 15.99% 861 7.20% 1777 30.21%
45-65 years 5382 37.62% 4159 35.31% 2893 47.57%
> 65 years 8116 46.39% 7974 57.49% 1567 22.22%
Sex < 0.001
Male 4791 34.25% 6831 56.13% 2157 36.84%
Female 11071 65.75% 6163 43.87% 4080 63.16%
Race/ethnicity < 0.001
Hispanic 1321 5.78% 582 3.08% 315 3.23%
Non-Hispanic White 12752 85.73% 11221 90.67% 5153 87.62%
Non-Hispanic Black 1354 5.92% 987 4.92% 634 7.00%
Non-Hispanic Other 435 2.57% 204 1.34% 135 2.14%
Education < 0.001
Less than high school degree 2679 13.73% 2537 17.50% 1427 21.33%
High school degree 4338 27.33% 3691 28.62% 2114 35.86%
More than high school degree 8845 58.94% 6766 53.88% 2696 42.80%
Marital status < 0.001
Married/Living with partner 7991 64.97% 7080 69.19% 2648 56.85%
Widowed/Divorced/Separated/Never married 7871 35.03% 5914 30.81% 3589 43.15%
Income level < 0.001
Low 1848 8.11% 1137 6.26% 1414 18.60%
Middle 8215 48.49% 7167 52.49% 3381 55.03%
High 5799 43.40% 4690 41.25% 1442 26.37%
Body mass index < 0.001
< 25 kg/m2 6087 38.62% 4521 33.79% 2885 45.61%
25-30 kg/m2 5549 35.01% 4992 39.15% 1960 32.12%
> 30 kg/m2 4226 26.37% 3481 27.06% 1392 22.28%
Physical activity < 0.001
Low 9927 59.51% 8083 59.74% 4378 69.52%
High 5935 40.49% 4911 40.26% 1859 30.48%
Alcohol intake < 0.001
Lifetime abstainer 5171 29.74% 1366 9.93% 681 10.28%
Former drinker 2972 17.97% 4001 28.92% 1589 25.34%
Current drinker 7648 51.83% 7539 60.53% 3915 63.71%
Self-rated health < 0.001
Excellent 2702 18.84% 1735 14.16% 595 9.65%
Very good 4306 28.46% 3282 25.89% 1337 22.37%
Good 5015 31.04% 4167 32.22% 1955 31.53%
Fair 2774 15.67% 2581 18.84% 1512 23.26%
Poor 1065 5.99% 1229 8.88% 838 13.19%
History of hypertension < 0.001
Yes 7835 46.52% 7081 52.97% 2632 40.77%
No 8027 53.48% 5913 47.03% 3605 59.23%
History of diabetes < 0.001
Yes 2317 13.83% 2286 16.96% 680 10.69%
No 13545 86.17% 10708 83.04% 5557 89.31%
History of CHD < 0.001
Yes 1466 9.04% 2065 16.24% 607 9.15%
No 14396 90.96% 10929 83.76% 5630 90.85%
History of stroke < 0.001
Yes 939 5.45% 992 7.45% 477 6.79%
No 14923 94.55% 12002 92.55% 5760 93.21%
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Abbreviations: CHD = coronary heart disease.

Among 35,093 cancer survivors, 11,066 died of all-causes (including 3,979 cancer and 2,156 CVD deaths) after a median follow-up of 13 years. The most common deaths occurred among survivors of breast (752 deaths), prostate (559 deaths), lung (467 deaths), colon (435 deaths), and non-melanoma skin (384 deaths) cancer survivors. Similarly, CVD deaths occurred mostly in breast (389 deaths) , prostate (348 deaths), and non-melanoma skin (334 deaths) cancer survivors (Figure 1 Analytic sample selection).

Figure 1.

Figure 1

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Analytic sample.

Smoking status

All-cause mortality

Among all survivors, current smokers had an 85%, 75% and 73% higher risk for all-cause, cancer, and CVD-related mortality when compared to never smokers. However, former smokers had a higher risk for all-cause (31%) and cancer mortality (37%), but not CVD mortality (see Figures 2, 3 and Table 2). For specific cancer sites, there was a 60% increase in all-cause mortality among current smokers who were survivors of bladder, breast, lung, colon, lymphoma and prostate cancer, and 130% increase in all-cause mortality among survivors of cervical, uterine, melanoma and non-melanoma cancer when compared to never smokers. Similarly, former smokers had a 27% higher risk for all-cause mortality when compared to select cancer survivors (i.e., breast, colon, lung, melanoma, prostate, uterine and non-melanoma skin cancer survivors) who never smoked. These relationships were stronger for cervical cancer survivors (Hazard Ratio [HR] = 1.58, 95% CI = 1.16 to 2.15) who never smoked, but no associations were observed in bladder and lymphoma cancer survivors (Figure 2-Current smoking and risk of all-cause mortality).

Figure 2.

Figure 2

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Current smoking and risk of all-cause mortality.

Figure 3.

Figure 3

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Former smoking and risk of all-cause mortality.

Table 2.

Cancer, CVD and other cause mortality among cancer survivors according to smoking status

Cancer sites Smoking status Subgroups Cancer mortality CVD mortality Other mortality
Deaths Person years HR (95% CI) P valuea Deaths Person years HR (95% CI) P valuea Deaths Person years HR (95% CI) P valuea
All sites
Never smoking 1386 15862 1 (Reference) 941 15862 1 (Reference) 2007 15862 1 (Reference)
Current smoking 825 6237 1.75 (1.57 to 1.95) < 0.001 292 6237 1.73 (1.47 to 2.05) < 0.001 770 6237 2.06 (1.83 to 2.33) < 0.001
< 10 cigarette per day 1.74 (1.50 to 2.03) < 0.001 1.83 (1.42 to 2.37) < 0.001 1.80 (1.50 to 2.16) < 0.001
≥ 10 cigarette per day 1.89 (1.67 to 2.14) < 0.001 1.79 (1.47 to 2.18) < 0.001 2.39 (2.09 to 2.75) < 0.001
Former smoking 1768 12994 1.37 (1.25 to 1.49) < 0.001 923 12994 1.08 (0.96 to 1.22) 0.194 2154 12994 1.38 (1.27 to 1.49) < 0.001
Quit smoking < 10 years 1.87 (1.66 to 2.10) < 0.001 1.50 (1.23 to 1.83) < 0.001 1.88 (1.65 to 2.14) < 0.001
Quit smoking 10-19 years 1.49 (1.31 to 1.68) < 0.001 1.26 (1.07 to 1.48) 0.006 1.42 (1.27 to 1.60) < 0.001
Quit smoking ≥ 20 years 1.09 (0.98 to 1.21) 0.122 0.91 (0.79 to 1.05) 0.204 1.21 (1.11 to 1.33) < 0.001
P for trend < 0.001 < 0.001 < 0.001
Bladder
Never smoking 23 210 1 (Reference) 17 210 1 (Reference) 47 210 1 (Reference)
Current smoking 34 181 1.62 (0.92 to 2.86) 0.092 13 181 1.11 (0.45 to 2.70) 0.824 38 181 1.37 (0.81 to 2.32) 0.242
< 10 cigarette per day 2.40 (1.07 to 5.38) 0.033 0.33 (0.07 to 1.57) 0.163 0.93 (0.39 to 2.25) 0.877
≥ 10 cigarette per day 1.73 (0.91 to 3.26) 0.092 1.41 (0.54 to 3.64) 0.48 0.68 (0.96 to 2.97) 0.071
Former smoking 86 501 1.11 (0.66 to 1.87) 0.682 50 501 1.29 (0.70 to 2.38) 0.419 124 501 1.18 (0.82 to 1.71) 0.366
Quit smoking < 10 years 2.11 (1.06 to 4.19) 0.033 0.98 (0.31 to 3.10) 0.978 1.59 (0.86 to 2.93) 0.135
Quit smoking 10-19 years 1.16 (0.60 to 2.22) 0.657 1.72 (0.83 to 3.59) 0.147 1.19 (0.73 to 1.96) 0.487
Quit smoking ≥ 20 years 0.86 (0.47 to 1.57) 0.612 1.20 (0.60 to 2.40) 0.615 1.15 (0.76 to 1.73) 0.507
P for trend 0.075 0.504 0.293
Breast
Never smoking 392 3608 1 (Reference) 240 3608 1 (Reference) 473 3608 1 (Reference)
Current smoking 120 807 1.47 (1.16 to 1.85) 0.001 39 807 1.79 (1.17 to 2.72) 0.007 112 807 2.46 (1.90 to 3.18) < 0.001
< 10 cigarette per day 1.53 (1.12 to 2.11) 0.008 2.16 (1.29 to 3.63) 0.004 1.83 (1.26 to 2.65) 0.002
≥ 10 cigarette per day 1.55 (1.15 to 2.10) 0.005 1.97 (1.08 to 3.58) 0.028 3.32 (2.43 to 4.54) < 0.001
Former smoking 240 1962 1.20 (1.00 to 1.45) 0.053 110 1962 0.95 (0.71 to 1.26) 0.702 299 1962 1.50 (1.25 to 1.81) < 0.001
Quit smoking < 10 years 1.31 (0.96 to 1.78) 0.086 1.89 (1.17 to 3.06) 0.01 1.90 (1.39 to 2.61) < 0.001
Quit smoking 10-19 years 1.51 (1.12 to 2.04) 0.007 0.87 (0.58 to 1.31) 0.516 1.20 (0.88 to 1.63) 0.241
Quit smoking ≥ 20 years 0.95 (0.72 to 1.24) 0.682 0.67 (0.44 to 1.02) 0.062 1.54 (1.23 to 1.94) < 0.001
P for trend 0.011 0.253 < 0.001
Cervix
Never smoking 41 1023 1 (Reference) 34 1023 1 (Reference) 56 1023 1 (Reference)
Current smoking 40 1170 1.67 (0.91 to 3.06) 0.098 16 1170 1.50 (0.68 to 3.34) 0.315 80 1170 3.66 (2.28 to 5.89) < 0.001
< 10 cigarette per day 1.43 (0.61 to 3.36) 0.407 2.36 (0.80 to 6.95) 0.119 2.54 (1.40 to 4.60) 0.002
≥ 10 cigarette per day 1.94 (1.03 to 3.63) 0.039 1.16 (0.49 to 2.80) 0.732 4.46 (2.67 to 7.43) < 0.001
Former smoking 32 664 1.44 (0.85 to 2.45) 0.172 22 664 0.96 (0.50 to 1.83) 0.895 71 664 2.08 (1.33 to 3.25) 0.001
Quit smoking < 10 years 1.73 (0.93 to 3.21) 0.085 1.39 (0.58 to 3.32) 0.463 2.39 (1.42 to 4.02) 0.001
Quit smoking 10-19 years 1.52 (0.62 to 3.68) 0.356 1.24 (0.40 to 3.85) 0.706 2.60 (1.50 to 4.51) 0.001
Quit smoking ≥ 20 years 1.15 (0.46 to 2.84) 0.765 0.54 (0.22 to 1.33) 0.179 1.65 (0.83 to 3.29) 0.156
P for trend 0.09 0.321 < 0.001
Colon
Never smoking 165 1133 1 (Reference) 107 1133 1 (Reference) 234 1133 1 (Reference)
Current smoking 63 335 1.33 (0.95 to 1.88) 0.098 22 335 1.81 (0.98 to 3.34) 0.06 53 335 1.46 (0.98 to 2.17) 0.062
< 10 cigarette per day 1.24 (0.74 to 2.08) 0.416 2.22 (0.93 to 5.29) 0.072 1.11 (0.50 to 2.46) 0.8
≥ 10 cigarette per day 1.38 (0.92 to 2.07) 0.114 1.62 (0.75 to 3.53) 0.22 1.79 (1.15 to 2.81) 0.011
Former smoking 207 1053 1.26 (0.99 to 1.61) 0.061 109 1053 1.17 (0.84 to 1.62) 0.342 214 1053 1.18 (0.89 to 1.55) 0.242
Quit smoking < 10 years 1.32 (0.88 to 2.00) 0.181 1.84 (1.02 to 3.32) 0.043 1.93 (1.16 to 3.21) 0.011
Quit smoking 10-19 years 1.18 (0.83 to 1.69) 0.349 1.15 (0.69 to 1.92) 0.578 1.40 (1.01 to 1.93) 0.042
Quit smoking ≥ 20 years 1.27 (0.98 to 1.66) 0.076 1.00 (0.68 to 1.47) 0.985 0.90 (0.68 to 1.20) 0.477
P for trend 0.13 0.059 0.004
Lung
Never smoking 58 172 1 (Reference) 8 172 1 (Reference) 23 172 1 (Reference)
Current smoking 115 248 1.24 (0.87 to 1.76) 0.242 15 248 1.13 (0.34 to 3.79) 0.837 39 248 3.78 (1.99 to 7.18) < 0.001
< 10 cigarette per day 1.09 (0.73 to 1.63) 0.683 1.87 (0.54 to 6.47) 0.32 3.62 (1.76 to 7.44) 0.001
≥ 10 cigarette per day 1.43 (0.95 to 2.15) 0.085 0.51 (0.10 to 2.62) 0.419 4.10 (1.94 to 8.67) < 0.001
Former smoking 294 714 1.09 (0.82 to 1.45) 0.538 47 714 1.15 (0.44 to 3.00) 0.771 141 714 2.27 (1.36 to 3.79) 0.002
Quit smoking < 10 years 1.11 (0.81 to 0.92) 0.522 1.15 (0.41 to 3.23) 0.79 2.50 (1.42 to 4.40) 0.002
Quit smoking 10-19 years 1.12 (0.78 to 1.59) 0.541 1.31 (0.46 to 3.75) 0.612 2.12 (1.20 to 3.75) 0.01
Quit smoking ≥ 20 years 1.05 (0.76 to 1.46) 0.751 0.91 (0.27 to 3.08) 0.877 2.15 (1.20 to 3.86) 0.01
P for trend 0.433 0.545 0.004
Lymphoma
Never smoking 72 475 1 (Reference) 23 475 1 (Reference) 54 475 1 (Reference)
Current smoking 39 176 1.69 (1.04 to 2.74) 0.035 4 176 0.81 (0.22 to 3.02) 0.751 24 176 1.92 (0.96 to 3.82) 0.065
< 10 cigarette per day 0.91 (0.43 to 1.93) 0.813 0.26 (0.02 to 2.94) 0.273 0.96 (0.27 to 3.34) 0.945
≥ 10 cigarette per day 2.21 (1.33 to 3.65) 0.002 0.91 (0.18 to 4.56) 0.904 2.35 (1.09 to 5.09) 0.03
Former smoking 70 349 1.01 (0.68 to 1.49) 0.976 20 349 1.09 (0.49 to 2.42) 0.838 44 349 0.97 (0.59 to 1.57) 0.886
Quit smoking < 10 years 1.15 (0.63 to 2.09) 0.651 0.73 (0.16 to 3.24) 0.677 0.89 (0.36 to 2.21) 0.799
Quit smoking 10-19 years 0.94 (0.51 to 1.73) 0.853 1.46 (0.53 to 4.06) 0.464 1.44 (0.74 to 2.80) 0.287
Quit smoking ≥ 20 years 0.93 (0.57 to 1.52) 0.782 0.98 (0.35 to 2.79) 0.973 0.79 (0.44 to 1.43) 0.432
P for trend 0.77 0.95 0.525
Melanoma
Never smoking 64 1036 1 (Reference) 53 1036 1 (Reference) 99 1036 1 (Reference)
Current smoking 40 349 2.31 (1.35 to 3.93) 0.002 9 349 1.34 (0.48 to 3.75) 0.572 39 349 2.15 (1.26 to 3.66) 0.005
< 10 cigarette per day 2.12 (1.02 to 4.44) 0.046 3.32 (0.84 to 13.17) 0.087 3.12 (1.39 to 7.02) 0.006
≥ 10 cigarette per day 2.34 (1.30 to 4.22) 0.005 0.86 (0.28 to 2.63) 0.789 2.29 (1.26 to 4.15) 0.006
Former smoking 80 823 1.18 (0.75 to 1.88) 0.473 50 823 1.05 (0.63 to 1.74) 0.85 112 823 1.50 (1.04 to 2.17) 0.031
Quit smoking < 10 years 1.04 (0.56 to 1.94) 0.897 1.39 (0.65 to 2.96) 0.396 2.94 (1.82 to 4.77) < 0.001
Quit smoking 10-19 years 1.71 (0.89 to 3.27) 0.107 0.83 (0.38 to 1.82) 0.647 1.20 (0.69 to 2.11) 0.515
Quit smoking ≥ 20 years 1.09 (0.64 to 1.86) 0.755 0.99 (0.55 to 1.79) 0.967 1.19 (0.81 to 1.75) 0.378
P for trend 0.389 0.74 0.003
Prostate
Never smoking 161 1411 1 (Reference) 112 1411 1 (Reference) 225 1411 1 (Reference)
Current smoking 86 427 1.95 (1.45 to 2.64) < 0.001 43 427 1.39 (0.89 to 2.16) 0.15 80 427 2.00 (1.39 to 2.88) < 0.001
< 10 cigarette per day 2.19 (1.52 to 3.16) < 0.001 0.91 (0.39 to 2.14) 0.832 1.50 (0.75 to 2.98) 0.251
≥ 10 cigarette per day 1.97 (1.32 to 2.95) 0.001 1.97 (1.24 to 3.13) 0.004 2.40 (1.63 to 3.54) < 0.001
Former smoking 312 2106 1.26 (1.00 to 1.59) 0.052 193 2106 0.96 (0.73 to 1.27) 0.77 426 2106 1.37 (1.11 to 1.70) 0.004
Quit smoking < 10 years 1.56 (1.07 to 2.27) 0.02 1.85 (1.12 to 3.05) 0.016 1.82 (1.29 to 2.56) 0.001
Quit smoking 10-19 years 1.65 (1.20 to 2.25) 0.002 0.89 (0.58 to 1.37) 0.587 1.72 (1.32 to 2.26) < 0.001
Quit smoking ≥ 20 years 1.07 (0.82 to 1.39) 0.619 0.85 (0.65 to 1.12) 0.257 1.22 (0.96 to 1.55) 0.101
P for trend 0.001 0.144 0.042
Non-melanoma skin
Never smoking 123 2998 1 (Reference) 145 2998 1 (Reference) 324 2998 1 (Reference)
Current smoking 81 803 3.01 (2.15 to 4.21) < 0.001 33 803 1.73 (1.07 to 2.81) 0.026 103 803 2.27 (1.69 to 3.05) < 0.001
< 10 cigarette per day 2.58 (1.49 to 4.46) 0.001 1.77 (0.89 to 3.53) 0.104 1.86 (1.21 to 2.86) 0.005
≥ 10 cigarette per day 3.44 (2.36 to 5.00) < 0.001 1.66 (0.93 to 2.98) 0.089 2.62 (1.84 to 3.72) < 0.001
Former smoking 180 2485 1.47 (1.12 to 1.94) 0.005 156 2485 1.12 (0.84 to 1.50) 0.429 353 2485 1.38 (1.15 to 1.66) 0.001
Quit smoking < 10 years 2.71 (1.84 to 3.99) < 0.001 1.14 (0.61 to 2.15) 0.677 1.93 (1.38 to 2.70) < 0.001
Quit smoking 10-19 years 1.65 (1.05 to 2.59) 0.031 1.75 (1.17 to 2.61) 0.006 1.63 (1.23 to 2.17) 0.001
Quit smoking ≥ 20 years 1.17 (0.85 to 1.59) 0.337 0.98 (0.71 to 1.36) 0.926 1.24 (1.01 to 1.53) 0.039
P for trend < 0.001 0.097 0.001
Uterine
Never smoking 65 935 1 (Reference) 64 935 1 (Reference) 145 935 1 (Reference)
Current smoking 41 549 2.57 (1.51 to 4.37) 0.001 48 549 2.78 (1.54 to 5.04) 0.001 66 549 2.96 (2.00 to 4.38) < 0.001
< 10 cigarette per day 2.26 (1.05 to 4.89) 0.038 1.65 (0.72 to 3.79) 0.237 3.55 (1.98 to 6.39) < 0.001
≥ 10 cigarette per day 3.14 (1.71 to 5.77) < 0.001 3.62 (1.85 to 7.09) < 0.001 2.58 (1.65 to 4.05) < 0.001
Former smoking 35 498 1.18 (0.76 to 1.85) 0.461 32 498 0.92 (0.54 to 1.56) 0.761 86 498 1.40 (1.01 to 1.96) 0.046
Quit smoking < 10 years 1.61 (0.76 to 3.43) 0.213 0.42 (0.15 to 1.14) 0.089 1.42 (0.79 to 2.57) 0.239
Quit smoking 10-19 years 2.15 (1.18 to 3.92) 0.012 0.97 (0.39 to 2.45) 0.952 1.39 (0.80 to 2.40) 0.245
Quit smoking ≥ 20 years 0.56 (0.27 to 1.17) 0.125 1.12 (0.59 to 2.15) 0.726 1.35 (0.88 to 2.07) 0.173
P for trend 0.073 0.366 0.342
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Abbreviations: CVD = cardiovascular disease; CI = confidence interval; HR = hazard ratio, CHD = coronary heart disease.

a

Adjusted for age, sex, race, education level, marital status, body mass index, physical activity, alcohol intake, income level, self-rated health, history of hypertension, diabetes, CHD, stroke and duration of cancer.

Cancer mortality

The HRs for cancer mortality ranged from 1.47 to 3.01 among current smokers who were survivors of non-melanoma skin (HR = 3.01, 95% CI = 2.15 to 4.21) and uterine cancer (HR = 2.57, 95% CI = 1.51 to 4.37), followed by survivors of melanoma (HR = 2.31, 95% CI = 1.35 to 3.93), prostate (HR = 1.95, 95% CI = 1.45 to 2.64), lymphoma (HR = 1.69, 95% CI = 1.04 to 2.74), and breast (HR = 1.47, 95% CI = 1.16 to 1.85) cancer. In contrast, former smokers who were survivors of on-melanoma skin cancer (HR = 1.47, 95% CI = 1.12 to 1.94) had a higher risk for cancer mortality than survivors who never smoked.

CVD mortality

For CVD mortality, current smokers had a higher risk of CVD mortality in uterine (HR = 2.78, 95% CI = 1.54 to 5.04), breast (HR = 1.79, 95% CI = 1.17 to 2.72), and non-melanoma skin cancer survivors (HR = 1.73, 95% CI = 1.07 to 2.81) when compared to those who never smoked. Former smokers, regardless of cancer diagnosis did not have a higher risk for CVD mortality when compared to never smokers (Figure 3 Former smoking and risk of all-cause mortality).

Smoking intensity

All-cause mortality

As summarized in Figure 4A, 4B and Table 2, when compared to those who never smoked, current smokers who smoked ≥ 10 cigarettes per day had a higher risk of all-cause (HR = 2.04, 95% CI = 1.87 to 2.22) and cancer (HR = 1.89, 95% CI = 1.67 to 2.14) mortality when compared to those who smoked < 10 cigarettes per day. For site-specific cancers, current smokers who smoked ≥ 10 cigarettes per day had a higher risk for all-cause mortality than those who smoked < 10 cigarettes per day for breast, cervix, lung, prostate, uterine and non-melanoma skin cancer survivors.

Figure 4.

Figure 4

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Cigarettes per day and risk of all-cause mortality among current smokers (A. Current smokers smoked < 10 cigarettes per day and risk of all-cause mortality; B. Current smokers smoked ≥ 10 cigarettes per day and risk of all-cause mortality). Time since smoking cesstions and risk of all-cause mortality among former smokers (C. Former smokers quit smoking < 10 years and risk of all-cause mortality; D. Former smokers quit smoking 10-19 years and risk of all-cause mortality; E. Former smokers quit smoking ≥ 20 years and risk of all-cause mortality).

Cancer mortality

When compared to those who never smoked, the risk for cancer mortality was higher for current smokers who smoked ≥ 10 cigarettes per day than those who smoked < 10 cigarettes per day for breast, melanoma, uterine and non-melanoma skin cancer survivors.

CVD mortality

There were no statistically significant differences between CVD mortality and cigarettes per day for current smokers in other select cancer sites survivors excepted in breast cancer survivors [Figure 4A, 4B Cigarettes per day and risk of all-cause mortality among current smokers. (A) Current smokers smoked < 10 cigarettes per day and risk of all-cause mortality; (B) Current smokers smoked ≥ 10 cigarettes per day and risk of all-cause mortality].

Time since smoking cessations

Figure 4C-E and Table 2 showed that the risk for all-cause mortality was higher for former smokers who had quit more recently than for those who had quit earlier (Ptrend < 0.001). For all-cause mortality, there were obvious dose-response relationships among former smokers as the quit time increased in those diagnosed with non-melanoma skin cancer (Ptrend < 0.001). For cancer mortality, there were no apparent dose-response relationships among former smokers as the quit time increased in any survivor groups. In addition, there was no apparent significant dose-response relationship between former smoking and the risk of CVD mortality [Figure 4C-E Time since smoking cessation and risk of all-cause mortality among former smokers. (C) Former smokers quit smoking < 10 years and risk of all-cause mortality; (D) Former smokers quit smoking 10-19 years and risk of all-cause mortality; (E) Former smokers quit smoking ≥ 20 years and risk of all-cause mortality].

Sensitivity analysis

When deaths within the first 2-years of follow-up were excluded for models examining associations between risk factors and all-cause mortality, the dose-response relationship was apparent for former smokers as the smoking quit time increased in lung cancer survivors (Ptrend < 0.001). Former smoking was associated with a higher risk for cancer mortality among breast (HR = 1.26, 95% CI = 1.04 to 1.54) cancer survivors when compared to those who never smoked. Current smoking was associated with a higher risk for cancer mortality among lung (HR = 1.58, 95% CI = 1.05 to 2.37) and colon (HR = 1.50, 95% CI = 1.06 to 2.13) cancer survivors when compared to those who never smoked. There were no statistically significant differences between former smoking and never smokers for the risk of all-cause mortality in lung cancer survivors. (Detailed in Table 3).

Table 3.

All-cause, cancer, CVD and other cause mortality among cancer survivors by cigarettes per day and time since quitting smoking after excluding individuals who died within the 2 years

Cancer sites Smoking status Subgroups All cause mortality Cancer mortality CVD mortality Other mortality
HR (95% CI) P valuea HR (95% CI) P valuea HR (95% CI) P valuea HR (95% CI) P valuea
All sites
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.96 (1.82 to 2.11) < 0.001 1.92 (1.72 to 2.15) < 0.001 1.83 (1.54 to 2.18) < 0.001 2.11 (1.87 to 2.38) < 0.001
< 10 cigarette per day 1.87 (1.68 to 2.07) < 0.001 1.89 (1.61 to 2.21) < 0.001 1.94 (1.49 to 2.52) < 0.001 1.82 (1.51 to 2.19) < 0.001
≥ 10 cigarette per day 2.18 (2.01 to 2.38) < 0.001 2.09 (1.85 to 2.37) < 0.001 1.92 (1.56 to 2.36) < 0.001 2.47 (2.15 to 2.84) < 0.001
Former smoking 1.31 (1.25 to 1.38) < 0.001 1.36 (1.25 to 1.49) < 0.001 1.09 (0.97 to 8.18) 0.162 1.38 (1.27 to 1.49) < 0.001
Quit smoking < 10 years 1.84 (1.70 to 1.99) < 0.001 1.89 (1.67 to 2.14) < 0.001 1.57 (1.28 to 1.92) < 0.001 1.91 (1.67 to 2.18) < 0.001
Quit smoking 10-19 years 1.42 (1.32 to 1.53) < 0.001 1.47 (1.29 to 1.68) < 0.001 1.30 (1.10 to 1.54) 0.002 1.44 (1.28 to 1.62) < 0.001
Quit smoking ≥ 20 years 1.10 (1.04 to 1.16) 0.001 1.09 (0.98 to 1.21) 0.133 0.89 (0.77 to 1.04) 0.139 1.21 (1.10 to 1.32) < 0.001
P for trend < 0.001 < 0.001 < 0.001 < 0.001
Bladder
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.52 (1.09 to 2.11) 0.013 1.72 (0.97 to 3.05) 0.062 1.41 (0.54 to 1.18) 0.479 1.39 (0.82 to 2.36) 0.216
< 10 cigarette per day 1.47 (0.85 to 2.55) 0.167 2.87 (1.28 to 6.41) 0.01 0.42 (0.09 to 2.05) 0.282 1.05 (0.43 to 2.56) 0.919
≥ 10 cigarette per day 1.74 (1.22 to 2.49) 0.003 1.78 (0.93 to 3.40) 0.079 1.76 (0.63 to 2.91) 0.281 1.66 (0.94 to 2.95) 0.082
Former smoking 1.18 (0.89 to 1.55) 0.246 0.95 (0.57 to 1.57) 0.828 1.59 (0.82 to 4.18) 0.168 1.16 (0.79 to 1.71) 0.442
Quit smoking < 10 years 1.58 (1.07 to 2.36) 0.023 1.73 (0.90 to 3.34) 0.102 1.26 (0.37 to 2.27) 0.71 1.46 (0.77 to 2.80) 0.247
Quit smoking 10-19 years 1.30 (0.89 to 1.90) 0.181 0.99 (0.50 to 1.94) 0.971 2.18 (1.01 to 1.71) 0.048 1.19 (0.71 to 1.98) 0.507
Quit smoking ≥ 20 years 1.06 (0.79 to 1.43) 0.69 0.73 (0.39 to 1.34) 0.309 1.39 (0.66 to 2.93 0.388 1.16 (0.76 to 1.77) 0.479
P for trend 0.058 0.192 0.215 0.402
Breast
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.90 (1.64 to 2.22) < 0.001 1.56 (1.22 to 1.98) < 0.001 1.84 (1.19 to 3.18) 0.007 2.57 (1.99 to 3.32) < 0.001
< 10 cigarette per day 1.78 (1.43 to 2.21) < 0.001 1.61 (1.15 to 2.26) 0.005 2.01 (1.14 to 2.53) 0.015 1.92 (1.33 to 2.78) 0.001
≥ 10 cigarette per day 2.22 (1.83 to 2.69) < 0.001 1.65 (1.22 to 2.24) 0.001 1.91 (1.02 to 2.56) 0.043 3.47 (2.54 to 4.74) < 0.001
Former smoking 1.30 (1.15 to 1.47) < 0.001 1.26 (1.04 to 1.54) 0.018 0.90 (0.66 to 1.18) 0.498 1.54 (1.27 to 1.85) < 0.001
Quit smoking < 10 years 1.58 (1.29 to 1.94) < 0.001 1.39 (1.02 to 1.91) 0.04 1.59 (0.98 to 1.60) 0.062 1.92 (1.39 to 2.65) < 0.001
Quit smoking 10-19 years 1.31 (1.08 to 1.59) 0.006 1.60 (1.18 to 2.18) 0.003 0.88 (0.57 to 1.34) 0.539 1.23 (0.91 to 1.67) 0.185
Quit smoking ≥ 20 years 1.16 (1.00 to 1.36) 0.057 0.97 (0.74 to 1.29) 0.847 0.69 (0.44 to 1.09) 0.115 1.58 (1.26 to 1.98) < 0.001
P for trend < 0.001 0.003 0.554 0.129
Cervix
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.50 (1.80 to 3.48) < 0.001 1.84 (0.99 to 3.42) 0.055 1.53 (0.67 to 1.18) 0.309 3.87 (2.44 to 6.14) < 0.001
< 10 cigarette per day 2.12 (1.35 to 3.32) 0.001 1.58 (0.67 to 3.72) 0.299 2.38 (0.79 to 3.17) 0.124 2.62 (1.39 to 4.92) 0.003
≥ 10 cigarette per day 2.86 (1.98 to 4.13) < 0.001 2.10 (1.10 to 4.00) 0.024 1.19 (0.49 to 4.88) 0.699 4.73 (2.88 to 7.76) < 0.001
Former smoking 1.61 (1.18 to 2.18) 0.003 1.29 (0.74 to 2.24) 0.363 0.98 (0.50 to 2.18) 0.95 2.30 (1.49 to 3.54) < 0.001
Quit smoking < 10 years 1.86 (1.29 to 2.66) 0.001 1.43 (0.73 to 2.82) 0.296 1.41 (0.59 to 2.37) 0.442 2.70 (1.62 to 4.49) < 0.001
Quit smoking 10-19 years 1.94 (1.26 to 3.00) 0.003 1.40 (0.55 to 3.56) 0.482 1.31 (0.40 to 3.22) 0.655 2.72 (1.54 to 4.80) 0.001
Quit smoking ≥ 20 years 1.27 (0.79 to 2.04) 0.316 1.12 (0.46 to 2.74) 0.803 0.54 (0.21 to 1.35) 0.187 1.88 (0.97 to 3.65) 0.063
P for trend < 0.001 0.264 0.295 0.006
Colon
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.51 (1.16 to 1.97) 0.002 1.50 (1.06 to 2.13) 0.023 1.99 (1.04 to 2.18) 0.038 1.44 (0.94 to 2.21) 0.09
< 10 cigarette per day 1.48 (0.93 to 2.34) 0.098 1.41 (0.83 to 2.40) 0.203 2.51 (1.07 to 2.90) 0.034 1.14 (0.49 to 2.66) 0.764
≥ 10 cigarette per day 1.63 (1.23 to 2.15) 0.001 1.56 (1.03 to 2.36) 0.036 1.76 (0.71 to 2.32) 0.219 1.80 (1.12 to 2.91) 0.016
Former smoking 1.18 (1.01 to 1.39) 0.039 1.26 (0.97 to 1.63) 0.087 1.14 (0.83 to 9.18) 0.423 1.18 (0.89 to 1.56) 0.249
Quit smoking < 10 years 1.80 (1.29 to 2.52) 0.001 1.43 (0.92 to 2.21) 0.111 1.98 (1.11 to 2.54) 0.022 2.02 (1.22 to 3.36) 0.007
Quit smoking 10-19 years 1.22 (1.00 to 1.49) 0.05 1.10 (0.75 to 1.61) 0.627 1.22 (0.72 to 1.05) 0.458 1.39 (0.99 to 1.94) 0.057
Quit smoking ≥ 20 years 1.00 (0.84 to 1.18) 0.966 1.26 (0.95 to 1.66) 0.108 0.91 (0.61 to 1.35) 0.637 0.90 (0.67 to 1.20) 0.475
P for trend < 0.001 0.123 0.03 0.092
Lung
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.94 (1.38 to 2.73) < 0.001 1.58 (1.05 to 2.37) 0.028 1.36 (0.34 to 1.18) 0.667 3.91 (2.02 to 7.60) < 0.001
< 10 cigarette per day 1.79 (1.24 to 2.58) 0.002 1.28 (0.79 to 2.05) 0.314 2.25 (0.56 to 2.96) 0.249 3.80 (1.75 to 8.27) 0.001
≥ 10 cigarette per day 2.14 (1.44 to 3.18) < 0.001 1.94 (1.24 to 3.03) 0.004 0.57 (0.08 to 3.02) 0.573 4.22 (1.94 to 9.19) < 0.001
Former smoking 1.46 (1.11 to 1.92) 0.006 1.17 (0.83 to 1.63) 0.371 1.43 (0.47 to 4.18) 0.529 2.50 (1.45 to 4.32) 0.001
Quit smoking < 10 years 1.53 (1.13 to 2.06) 0.006 1.20 (0.83 to 1.73) 0.335 1.57 (0.48 to 2.09) 0.452 2.78 (1.50 to 5.14) 0.001
Quit smoking 10-19 years 1.47 (1.09 to 1.98) 0.011 1.18 (0.78 to 1.78) 0.439 1.62 (0.49 to 1.36) 0.427 2.28 (1.25 to 4.17) 0.008
Quit smoking ≥ 20 years 1.35 (1.00 to 1.81) 0.049 1.11 (0.76 to 1.61) 0.6 0.80 (0.21 to 3.02) 0.74 2.41 (1.31 to 4.46) 0.005
P for trend 0.002 0.198 0.241 0.193
Lymphoma
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.01 (1.39 to 2.91) < 0.001 1.83 (1.08 to 3.10) 0.026 1.00 (0.27 to 4.18) 0.995 2.55 (1.35 to 4.80) 0.004
< 10 cigarette per day 1.08 (0.59 to 1.98) 0.8 1.04 (0.47 to 2.28) 0.924 0.31 (0.02 to 1.15) 0.372 1.36 (0.41 to 4.52) 0.619
≥ 10 cigarette per day 2.59 (1.77 to 3.79) < 0.001 2.38 (1.37 to 4.13) 0.002 1.18 (0.24 to 3.75) 0.833 3.25 (1.60 to 6.62) 0.001
Former smoking 1.10 (0.82 to 1.47) 0.537 1.06 (0.70 to 1.60) 0.789 1.06 (0.45 to 1.18) 0.891 1.12 (0.69 to 1.82) 0.632
Quit smoking < 10 years 1.14 (0.70 to 1.83) 0.603 1.19 (0.64 to 2.23) 0.576 0.96 (0.22 to 1.09) 0.953 1.15 (0.47 to 2.81) 0.766
Quit smoking 10-19 years 1.31 (0.86 to 1.99) 0.207 0.90 (0.45 to 1.79) 0.755 1.56 (0.51 to 1.71) 0.433 1.71 (0.86 to 3.37) 0.123
Quit smoking ≥ 20 years 1.00 (0.69 to 1.45) 0.998 1.02 (0.62 to 1.69) 0.934 0.82 (0.25 to 2.74) 0.748 0.96 (0.53 to 1.73) 0.889
P for trend 0.425 0.678 0.806 0.855
Melanoma
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.08 (1.44 to 3.01) < 0.001 2.39 (1.38 to 4.12) 0.002 1.46 (0.52 to 9.18) 0.468 2.20 (1.25 to 3.86) 0.006
< 10 cigarette per day 2.87 (1.77 to 4.66) < 0.001 2.25 (1.07 to 4.73) 0.032 3.60 (0.92 to 4.15) 0.067 3.41 (1.47 to 7.88) 0.004
≥ 10 cigarette per day 2.02 (1.33 to 3.09) 0.001 2.40 (1.30 to 4.43) 0.005 0.93 (0.30 to 3.87) 0.904 2.36 (1.27 to 4.40) 0.007
Former smoking 1.29 (1.01 to 1.65) 0.04 1.10 (0.71 to 1.71) 0.677 1.14 (0.69 to 4.18) 0.603 1.48 (1.01 to 2.16) 0.045
Quit smoking < 10 years 1.98 (1.39 to 2.83) < 0.001 1.07 (0.57 to 2.02) 0.825 1.39 (0.64 to 2.01) 0.403 3.07 (1.88 to 5.01) < 0.001
Quit smoking 10-19 years 1.24 (0.85 to 1.80) 0.259 1.60 (0.82 to 3.09) 0.164 0.92 (0.42 to 1.03) 0.841 1.10 (0.61 to 1.99) 0.74
Quit smoking ≥ 20 years 1.09 (0.84 to 1.42) 0.509 0.97 (0.57 to 1.64) 0.904 1.10 (0.61 to 1.99) 0.761 1.15 (0.77 to 1.71) 0.504
P for trend 0.002 0.379 0.617 0.002
Prostate
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.91 (1.51 to 2.41) < 0.001 2.14 (1.58 to 2.89) < 0.001 1.43 (0.91 to 4.18) 0.125 1.97 (1.35 to 2.86) < 0.001
< 10 cigarette per day 1.65 (1.13 to 2.42) 0.01 2.31 (1.60 to 3.33) < 0.001 0.99 (0.42 to 2.34) 0.979 1.41 (0.68 to 2.90) 0.356
≥ 10 cigarette per day 2.23 (1.74 to 2.86) < 0.001 2.19 (1.46 to 3.28) < 0.001 2.02 (1.26 to 2.24) 0.004 2.41 (1.63 to 3.56) < 0.001
Former smoking 1.24 (1.07 to 1.43) 0.005 1.27 (1.00 to 1.61) 0.05 0.98 (0.73 to 1.18) 0.885 1.35 (1.09 to 1.68) 0.006
Quit smoking < 10 years 1.76 (1.40 to 2.23) < 0.001 1.51 (1.03 to 2.21) 0.036 2.03 (1.22 to 2.38) 0.007 1.85 (1.30 to 2.62) 0.001
Quit smoking 10-19 years 1.50 (1.22 to 1.83) < 0.001 1.62 (1.18 to 2.24) 0.003 0.96 (0.62 to 1.47) 0.838 1.73 (1.32 to 2.28) < 0.001
Quit smoking ≥ 20 years 1.08 (0.93 to 1.26) 0.302 1.10 (0.84 to 1.44) 0.478 0.84 (0.63 to 1.12) 0.224 1.20 (0.95 to 1.53) 0.129
P for trend < 0.001 0.002 0.068 0.036
Non-melanoma skin
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.39 (1.94 to 2.95) < 0.001 3.09 (2.20 to 4.33) < 0.001 1.89 (1.17 to 3.18) 0.01 2.25 (1.67 to 3.02) < 0.001
< 10 cigarette per day 2.04 (1.52 to 2.74) < 0.001 2.64 (1.52 to 4.57) 0.001 1.94 (0.98 to 2.87) 0.059 1.81 (1.17 to 2.82) 0.009
≥ 10 cigarette per day 2.69 (2.10 to 3.45) < 0.001 3.52 (2.41 to 5.13) < 0.001 1.82 (1.02 to 3.24) 0.043 2.60 (1.83 to 3.70) < 0.001
Former smoking 1.32 (1.17 to 1.50) < 0.001 1.47 (1.12 to 1.94) 0.006 1.13 (0.84 to 1.18) 0.417 1.35 (1.12 to 1.63) 0.002
Quit smoking < 10 years 1.92 (1.52 to 2.44) < 0.001 2.63 (1.78 to 3.89) < 0.001 1.22 (0.64 to 2.30) 0.543 1.91 (1.36 to 2.68) < 0.001
Quit smoking 10-19 years 1.68 (1.39 to 2.04) < 0.001 1.66 (1.05 to 2.63) 0.029 1.84 (1.23 to 2.76) 0.003 1.63 (1.23 to 2.17) 0.001
Quit smoking ≥ 20 years 1.14 (0.99 to 1.31) 0.072 1.17 (0.85 to 1.61) 0.322 0.96 (0.69 to 1.35) 0.826 1.21 (0.98 to 1.49) 0.08
P for trend < 0.001 < 0.001 0.061 0.001
Uterine
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.93 (2.19 to 3.92) < 0.001 2.91 (1.69 to 5.00) < 0.001 2.84 (1.56 to 2.18) 0.001 3.08 (2.08 to 4.57) < 0.001
< 10 cigarette per day 2.93 (1.89 to 4.54) < 0.001 2.78 (1.29 to 5.96) 0.009 1.71 (0.76 to 4.88) 0.195 3.64 (2.00 to 6.62) < 0.001
≥ 10 cigarette per day 3.00 (2.15 to 4.16) < 0.001 3.36 (1.79 to 6.31) < 0.001 3.66 (1.82 to 4.35) < 0.001 2.75 (1.75 to 4.31) < 0.001
Former smoking 1.26 (0.98 to 1.61) 0.068 1.28 (0.80 to 2.06) 0.308 0.92 (0.53 to 3.18) 0.747 1.44 (1.03 to 2.02) 0.032
Quit smoking < 10 years 1.26 (0.85 to 1.87) 0.246 1.86 (0.88 to 3.93) 0.105 0.43 (0.16 to 1.17) 0.098 1.50 (0.83 to 2.71) 0.18
Quit smoking 10-19 years 1.44 (0.96 to 2.15) 0.079 2.19 (1.16 to 4.13) 0.015 0.90 (0.34 to 2.39) 0.83 1.41 (0.81 to 2.45) 0.221
Quit smoking ≥ 20 years 1.14 (0.83 to 1.58) 0.422 0.61 (0.29 to 1.32) 0.209 1.14 (0.60 to 2.18) 0.695 1.38 (0.90 to 2.14) 0.143
P for trend 0.042 0.032 0.352 0.293
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Abbreviations: CVD = cardiovascular disease; CI = confidence interval; HR = hazard ratio, CHD = coronary heart disease.

a

Adjusted for age, sex, race, education level, marital status, body mass index, physical activity, alcohol intake, income level, self-rated health, history of hypertension, diabetes, CHD, stroke and duration of cancer.

Excluding patients with a CVD history, there was a 57% increase in all-cause mortality among former smokers who were diagnosed with bladder cancer and a 91% increase in CVD mortality among all cancer survivors when compared to never smokers. Current smoking was associated with a higher risk for cancer mortality in bladder (HR = 2.12, 95% CI = 1.05 to 4.30) and colon (HR = 1.49, 95% CI = 1.03 to 2.15) cancer survivors when compared to those who never smoked. (Detailed in Table 4).

Table 4.

All-cause, cancer, CVD and other cause mortality among cancer survivors by cigarettes per day and time since quitting smoking after excluding participants with CVD history

Cancer sites Smoking status Subgroups All cause mortality Cancer mortality CVD mortality Other mortality
HR (95% CI) P valuea HR (95% CI) P valuea HR (95% CI) P valuea HR (95% CI) P valuea
All cancer sites
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.87 (1.72 to 2.02) < 0.001 1.72 (1.51 to 1.94) < 0.001 1.91 (1.57 to 2.33) < 0.001 2.09 (1.82 to 2.38) < 0.001
< 10 cigarette per day 1.77 (1.56 to 2.00) < 0.001 1.69 (1.42 to 2.02) < 0.001 1.97 (1.45 to 2.67) < 0.001 1.77 (1.43 to 2.20) < 0.001
≥ 10 cigarette per day 2.06 (1.87 to 2.26) < 0.001 1.85 (1.61 to 2.14) < 0.001 1.99 (1.57 to 2.52) < 0.001 2.40 (2.06 to 2.80) < 0.001
Former smoking 1.34 (1.26 to 1.42) < 0.001 1.39 (1.26 to 1.53) < 0.001 1.18 (1.57 to 1.37) 0.025 1.35 (1.23 to 1.48) < 0.001
Quit smoking < 10 years 1.86 (1.72 to 2.01) < 0.001 1.88 (1.65 to 2.15) < 0.001 1.74 (1.39 to 2.18) < 0.001 1.80 (1.59 to 2.04) < 0.001
Quit smoking 10-19 years 1.42 (1.30 to 1.55) < 0.001 1.46 (1.27 to 1.67) < 0.001 1.32 (1.08 to 1.63) 0.008 1.44 (1.25 to 1.67) < 0.001
Quit smoking ≥ 20 years 1.11 (1.04 to 1.19) 0.003 1.10 (0.98 to 1.23) 0.106 0.98 (0.81 to 1.18) 0.814 1.18 (1.05 to 1.32) 0.004
P for trend < 0.001 < 0.001 < 0.001 < 0.001
Bladder
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.58 (1.06 to 2.37) 0.026 2.12 (1.05 to 4.30) 0.036 1.64 (0.44 to 6.22) 0.462 1.23 (1.65 to 2.31) 0.52
< 10 cigarette per day 1.37 (0.62 to 3.00) 0.433 2.32 (0.64 to 8.41) 0.2 0.88 (0.11 to 7.08) 0.903 0.90 (0.27 to 3.02) 0.864
≥ 10 cigarette per day 1.89 (1.24 to 2.88) 0.003 2.32 (1.14 to 4.73) 0.021 2.09 (0.56 to 7.83) 0.273 1.51 (0.77 to 2.93) 0.226
Former smoking 1.57 (1.13 to 2.18) 0.007 1.65 (0.90 to 3.03) 0.107 1.96 (0.72 to 5.37) 0.19 1.39 (0.89 to 2.17) 0.151
Quit smoking < 10 years 2.21 (1.37 to 3.56) 0.001 2.87 (1.32 to 6.20) 0.008 1.64 (0.39 to 6.88) 0.499 1.71 (0.78 to 3.73) 0.176
Quit smoking 10-19 years 1.47 (0.92 to 2.34) 0.104 1.40 (0.66 to 2.97) 0.372 1.52 (0.43 to 5.33) 0.51 1.33 (0.73 to 2.41) 0.347
Quit smoking ≥ 20 years 1.62 (1.13 to 2.32) 0.009 1.23 (0.60 to 2.50) 0.568 2.51 (0.91 to 6.91) 0.075 1.55 (0.92 to 2.62) 0.099
P for trend 0.009 0.002 0.636 0.983
Breast
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.78 (1.50 to 2.11) < 0.001 1.36 (1.05 to 1.75) 0.02 1.69 (1.01 to 2.80) 0.044 2.87 (2.09 to 3.94) < 0.001
< 10 cigarette per day 1.62 (1.26 to 2.07) < 0.001 1.36 (0.95 to 1.94) 0.095 2.06 (1.06 to 3.99) 0.034 1.98 (1.28 to 3.07) 0.002
≥ 10 cigarette per day 2.11 (1.69 to 2.62) < 0.001 1.45 (1.05 to 2.00) 0.025 1.71 (0.85 to 3.46) 0.131 4.06 (2.77 to 5.95) < 0.001
Former smoking 1.27 (1.11 to 1.45) 0.001 1.21 (0.99 to 1.47) 0.06 0.88 (0.62 to 1.27) 0.507 1.53 (1.23 to 1.92) < 0.001
Quit smoking < 10 years 1.46 (1.16 to 1.84) 0.002 1.21 (0.87 to 1.69) 0.249 2.04 (1.17 to 3.58) 0.012 1.69 (1.10 to 2.59) 0.016
Quit smoking 10-19 years 1.23 (0.99 to 1.53) 0.059 1.50 (1.10 to 2.04) 0.011 0.83 (0.48 to 1.44) 0.509 1.13 (0.77 to 1.64) 0.534
Quit smoking ≥ 20 years 1.19 (1.00 to 1.42) 0.049 1.01 (0.76 to 1.35) 0.93 0.58 (0.32 to 1.05) 0.074 1.70 (1.32 to 2.19) < 0.001
P for trend 0.001 0.04 0.303 0.449
Cervix
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.72 (1.87 to 3.97) < 0.001 1.89 (0.96 to 3.71) 0.067 3.01 (1.32 to 6.88) 0.009 3.73 (2.18 to 6.38) < 0.001
< 10 cigarette per day 2.17 (1.27 to 3.71) 0.005 1.65 (0.64 to 4.22) 0.296 4.26 (1.49 to 12.18) 0.007 2.18 (0.99 to 4.81) 0.054
≥ 10 cigarette per day 3.17 (2.13 to 4.72) < 0.001 2.15 (1.05 to 4.38) 0.035 2.63 (1.04 to 6.65) 0.041 4.55 (2.61 to 7.96) < 0.001
Former smoking 2.08 (1.48 to 2.92) < 0.001 1.70 (0.99 to 2.94) 0.056 1.91 (0.91 to 4.02) 0.087 2.72 (1.65 to 4.49) < 0.001
Quit smoking < 10 years 2.17 (1.44 to 3.27) < 0.001 1.82 (0.92 to 3.59) 0.085 1.89 (0.63 to 5.69) 0.256 2.83 (1.58 to 5.07) < 0.001
Quit smoking 10-19 years 2.39 (1.46 to 3.92) 0.001 1.95 (0.79 to 4.80) 0.146 5.17 (1.64 to 16.29) 0.005 2.21 (1.06 to 4.63) 0.036
Quit smoking ≥ 20 years 1.93 (1.15 to 3.24) 0.013 1.49 (0.59 to 3.74) 0.399 0.74 (0.23 to 2.41) 0.617 3.08 (1.49 to 6.35) 0.002
P for trend < 0.001 0.091 0.003 0.01
Colon
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.57 (1.19 to 2.06) 0.001 1.49 (1.03 to 2.15) 0.032 2.60 (1.32 to 5.10) 0.006 1.41 (0.88 to 2.24) 0.151
< 10 cigarette per day 1.45 (0.88 to 2.40) 0.148 1.56 (0.91 to 2.69) 0.106 3.20 (1.20 to 8.55) 0.021 0.78 (0.23 to 2.59) 0.683
≥ 10 cigarette per day 1.64 (1.25 to 2.16) < 0.001 1.43 (0.92 to 2.22) 0.108 2.33 (1.05 to 5.19) 0.038 1.84 (1.13 to 3.02) 0.015
Former smoking 1.13 (0.96 to 1.32) 0.137 1.22 (0.94 to 1.60) 0.139 1.48 (0.98 to 2.24) 0.066 0.95 (0.72 to 1.25) 0.709
Quit smoking < 10 years 1.33 (1.03 to 1.73) 0.03 1.24 (0.78 to 1.97) 0.358 2.27 (1.12 to 4.56) 0.022 1.09 (0.69 to 1.72) 0.708
Quit smoking 10-19 years 1.25 (1.01 to 1.54) 0.042 1.13 (0.76 to 1.66) 0.545 1.43 (0.77 to 2.64) 0.255 1.31 (0.92 to 1.87) 0.128
Quit smoking ≥ 20 years 1.02 (0.84 to 1.24) 0.873 1.26 (0.94 to 1.68) 0.116 1.28 (0.78 to 2.10) 0.319 0.78 (0.55 to 1.10) 0.158
P for trend 0.004 0.263 0.011 0.919
Lung
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.82 (1.31 to 2.52) < 0.001 1.36 (0.92 to 2.01) 0.124 1.56 (0.32 to 7.71) 0.582 4.82 (2.38 to 9.77) < 0.001
< 10 cigarette per day 1.67 (1.16 to 2.40) 0.006 1.14 (0.73 to 1.78) 0.576 2.16 (0.35 to 13.39) 0.407 5.00 (2.22 to 11.25) < 0.001
≥ 10 cigarette per day 2.06 (1.40 to 3.01) < 0.001 1.70 (1.09 to 2.67) 0.02 1.00 (0.14 to 6.94) 0.996 4.96 (2.12 to 11.60) < 0.001
Former smoking 1.42 (1.09 to 1.86) 0.01 1.15 (0.83 to 1.59) 0.405 1.87 (0.59 to 5.91) 0.287 2.50 (1.37 to 4.54) 0.003
Quit smoking < 10 years 1.49 (1.11 to 2.01) 0.008 1.18 (0.82 to 1.68) 0.368 2.37 (0.74 to 7.54) 0.145 2.92 (1.50 to 5.68) 0.002
Quit smoking 10-19 years 1.44 (1.06 to 1.95) 0.019 1.27 (0.86 to 1.89) 0.232 1.72 (0.44 to 6.65) 0.432 2.12 (1.05 to 4.27) 0.035
Quit smoking ≥ 20 years 1.27 (0.92 to 1.77) 0.145 1.02 (0.68 to 1.52) 0.933 1.23 (0.29 to 5.24) 0.777 2.39 (1.18 to 4.82) 0.015
P for trend 0.008 0.201 0.083 0.225
Lymphoma
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.66 (1.09 to 2.51) 0.017 1.40 (0.83 to 2.37) 0.211 1.99 (0.52 to 7.54) 0.313 2.61 (1.21 to 5.67) 0.015
< 10 cigarette per day 0.61 (0.29 to 1.27) 0.185 0.61 (0.26 to 1.44) 0.258 0.79 (0.09 to 6.98) 0.829 0.60 (0.10 to 3.65) 0.577
≥ 10 cigarette per day 2.23 (1.45 to 3.41) < 0.001 1.91 (1.11 to 3.28) 0.02 1.81 (0.35 to 9.25) 0.477 3.41 (1.47 to 7.88) 0.004
Former smoking 1.07 (0.77 to 1.49) 0.701 1.05 (0.67 to 1.64) 0.837 1.39 (0.49 to 3.93) 0.529 1.14 (0.65 to 2.02) 0.644
Quit smoking < 10 years 1.02 (0.59 to 1.76) 0.949 1.12 (0.59 to 2.10) 0.73 0.96 (0.12 to 7.45) 0.971 0.95 (0.34 to 2.70) 0.929
Quit smoking 10-19 years 1.29 (0.83 to 2.01) 0.257 1.02 (0.51 to 2.04) 0.955 1.96 (0.51 to 7.61) 0.327 1.79 (0.78 to 4.15) 0.171
Quit smoking ≥ 20 years 0.99 (0.65 to 1.49) 0.945 0.98 (0.57 to 1.70) 0.955 1.33 (0.34 to 5.17) 0.675 0.89 (0.43 to 1.83) 0.742
P for trend 0.744 0.868 0.636 0.86
Melanoma
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.23 (1.48 to 3.36) < 0.001 2.08 (1.12 to 3.83) 0.02 1.90 (0.52 to 6.98) 0.33 2.49 (1.32 to 4.70) 0.005
< 10 cigarette per day 3.09 (1.70 to 5.60) < 0.001 1.78 (0.69 to 4.58) 0.229 6.93 (1.40 to 34.28) 0.018 3.90 (1.53 to 9.95) 0.005
≥ 10 cigarette per day 2.20 (1.42 to 3.40) < 0.001 2.13 (1.08 to 4.21) 0.029 0.89 (0.17 to 4.60) 0.894 2.65 (1.37 to 5.13) 0.004
Former smoking 1.33 (1.01 to 1.76) 0.046 1.34 (0.81 to 2.21) 0.249 1.50 (0.84 to 2.67) 0.172 1.26 (0.80 to 2.01) 0.32
Quit smoking < 10 years 1.52 (0.98 to 2.36) 0.061 1.30 (0.65 to 2.60) 0.453 1.21 (0.40 to 3.71) 0.736 1.76 (0.86 to 3.60) 0.118
Quit smoking 10-19 years 1.41 (0.93 to 2.14) 0.108 1.80 (0.87 to 3.73) 0.111 0.88 (0.28 to 2.81) 0.83 1.30 (0.69 to 2.42) 0.417
Quit smoking ≥ 20 years 1.27 (0.93 to 1.73) 0.127 1.23 (0.69 to 2.18) 0.487 1.76 (0.93 to 3.34) 0.084 1.15 (0.68 to 1.93) 0.6
P for trend 0.059 0.25 0.741 0.748
Prostate
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 1.86 (1.45 to 2.39) < 0.001 1.82 (1.28 to 2.57) 0.001 1.51 (0.87 to 2.60) 0.14 2.02 (1.34 to 3.03) 0.001
< 10 cigarette per day 1.84 (1.30 to 2.60) 0.001 2.11 (1.31 to 3.38) 0.002 0.95 (0.32 to 2.81) 0.927 1.81 (0.90 to 3.60) 0.094
≥ 10 cigarette per day 2.02 (1.49 to 2.74) < 0.001 1.81 (1.16 to 2.82) 0.009 2.05 (1.13 to 3.73) 0.019 2.14 (1.29 to 3.55) 0.003
Former smoking 1.21 (1.04 to 1.41) 0.014 1.24 (0.96 to 1.61) 0.104 1.07 (0.76 to 1.51) 0.701 1.24 (0.98 to 1.57) 0.071
Quit smoking < 10 years 1.75 (1.39 to 2.20) < 0.001 1.58 (1.06 to 2.36) 0.024 2.37 (1.36 to 4.13) 0.002 1.61 (1.13 to 2.31) 0.009
Quit smoking 10-19 years 1.58 (1.25 to 1.99) < 0.001 1.54 (1.05 to 2.27) 0.029 0.92 (0.49 to 1.74) 0.805 1.93 (1.41 to 2.63) < 0.001
Quit smoking ≥ 20 years 1.03 (0.87 to 1.21) 0.748 1.06 (0.80 to 1.42) 0.673 0.90 (0.61 to 1.31) 0.574 1.04 (0.80 to 1.36) 0.766
P for trend < 0.001 0.004 0.026 0.168
Non-melanoma skin
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 2.34 (1.84 to 2.96) < 0.001 3.68 (2.49 to 5.44) < 0.001 1.89 (1.09 to 3.28) 0.024 1.92 (1.37 to 2.69) < 0.001
< 10 cigarette per day 1.85 (1.30 to 2.63) 0.001 3.09 (1.72 to 5.54) < 0.001 1.60 (0.74 to 3.46) 0.235 1.39 (0.80 to 2.42) 0.242
≥ 10 cigarette per day 2.75 (2.07 to 3.65) < 0.001 4.30 (2.77 to 6.69) < 0.001 2.02 (1.01 to 4.04) 0.047 2.35 (1.59 to 3.47) < 0.001
Former smoking 1.39 (1.19 to 1.63) < 0.001 1.87 (1.35 to 2.57) < 0.001 1.10 (0.77 to 1.58) 0.588 1.31 (1.04 to 1.65) 0.022
Quit smoking < 10 years 2.27 (1.75 to 2.94) < 0.001 3.47 (2.23 to 5.40) < 0.001 1.66 (0.85 to 3.26) 0.138 1.99 (1.36 to 2.93) < 0.001
Quit smoking 10-19 years 1.77 (1.38 to 2.26) < 0.001 2.18 (1.30 to 3.66) 0.003 1.69 (0.99 to 2.87) 0.054 1.60 (1.12 to 2.30) 0.01
Quit smoking ≥ 20 years 1.13 (0.95 to 1.35) 0.171 1.40 (0.96 to 2.04) 0.077 0.88 (0.58 to 1.35) 0.564 1.12 (0.86 to 1.46) 0.394
P for trend < 0.001 < 0.001 0.05 0.003
Uterine
Never smoking 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference)
Current smoking 3.44 (2.48 to 4.78) < 0.001 3.17 (1.84 to 5.46) < 0.001 3.49 (1.52 to 8.04) 0.003 3.62 (2.27 to 5.79) < 0.001
< 10 cigarette per day 3.39 (2.04 to 5.64) < 0.001 2.36 (1.01 to 5.54) 0.048 2.58 (0.86 to 7.75) 0.09 4.36 (2.22 to 8.58) < 0.001
≥ 10 cigarette per day 3.55 (2.50 to 5.06) < 0.001 4.17 (2.16 to 8.05) < 0.001 4.17 (1.63 to 10.70) 0.003 3.16 (1.90 to 5.24) < 0.001
Former smoking 1.33 (1.00 to 1.78) 0.053 1.33 (0.81 to 2.19) 0.26 1.16 (0.64 to 2.11) 0.615 1.40 (0.93 to 2.11) 0.104
Quit smoking < 10 years 1.17 (0.69 to 2.00) 0.556 1.67 (0.71 to 3.91) 0.235 0.30 (0.06 to 1.45) 0.134 1.36 (0.66 to 2.80) 0.41
Quit smoking 10-19 years 1.65 (1.07 to 2.52) 0.022 2.25 (1.11 to 4.56) 0.025 1.92 (0.73 to 5.01) 0.184 1.34 (0.70 to 2.54) 0.379
Quit smoking ≥ 20 years 1.22 (0.81 to 1.81) 0.338 0.72 (0.30 to 1.70) 0.455 1.31 (0.62 to 2.78) 0.479 1.40 (0.82 to 2.37) 0.215
P for trend 0.097 0.058 0.868 0.301
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Abbreviations: CVD = cardiovascular disease; CI = confidence interval; HR = hazard ratio, CHD = coronary heart disease.

a

Adjusted for age, sex, race, education level, marital status, body mass index, physical activity, alcohol intake, income level, self-rated health, history of hypertension, diabetes, CHD, stroke and duration of cancer.

Discussion

This large prospective study showed that cancer survivors who reported being current or former smokers had a higher risk for all-cause and cancer mortality when compared with those who never smoked, but effects varied substantially by cancer site, especially for breast, prostate, and non-melanoma skin cancer survivors. Compared to nonsmokers, risk of CVD mortality increased among current smokers diagnosed with breast, non-melanoma skin and uterine cancer. However, there were no differences between former and never smokers for CVD mortality. Also, smoking cessation appears to benefit those with longer quit times as observed by the decreasing risk of mortality, especially for non-melanoma skin cancer survivors.

In the present study, we observed that current or former smokers had a higher risk of all-cause mortality when compared to nonsmokers among cancer survivors, similar to what was observed in a recent study [28]. The associations observed here between smoking status and all-cause mortality among colon and prostate cancer survivors was lower than what was observed elsewhere [13,19]. The difference might be explained by the statistical methods such as adjusting for lag time, family history of colon cancer, tumor stage and first course of cancer treatment in our models. Our study sheds new insight on the relationships between smoking status and all-cause mortality for bladder, lymphoma, melanoma, uterine and non-melanoma skin cancer survivors. In effort to advance our understanding of these relationships, future studies should consider examining the relationship smoking and mortality among various cancer survivor populations.

Previous studies have indicated that breast cancer survivors who report varying smoking histories have the same risk for cancer mortality [29]. However, here, we observed a different pattern of relationships. In particular, current smokers had higher risk for cancer mortality than never smokers. Similar associations were observed for prostate cancer survivors, with our study showing higher hazard ratios than what was observed in another prospective cohort study [14]. Conversely, we did not observe significant associations in cervical survivors, a finding which differs from what others have reported [21].

In our study, there was no dose-response relationships between duration of smoking cessation and risk of cancer mortality in prostate cancer survivors, consistent with a previous study [14], but a greater number of cigarettes per day was associated with a significantly increased risk of all-cause mortality. Significant dose-response association for breast cancer mortality was observed for number of cigarettes smoked per day (≤ 5, 6-10, 11-15 and ≥ 16) [30]. In particular, our study found the risk of all-cause and cancer mortality increased as the cigarettes per day increased (< 10 and ≥ 10). Besides, current smoking had the highest risk of all-cause mortality with daily cigarette consumption among cervical cancer survivors for cancer mortality, but another study found that both moderate and high daily cigarette consumption resulted in the highest risk for cervical cancer mortality [21]. We did not found any significant association between number of cigarettes per day and cancer mortality among colon cancer survivors, which differs from a previous study [13]. The dose-response relationship between duration of smoking cessation or cigarettes per day and risk of all-cause mortality was significant among non-melanoma skin cancer survivors, which was not reported previously.

Several potential mechanisms could contribute to the associations we observed between smoking and increased risk of all-cause mortality. In particular, smoking decreases the effectiveness of cancer treatments [31-33]. Studies have also shown that smoking increases the probability of recurrence and distant metastases [34,35] and increases the risk for second primary tumors [36], and premature mortality in cancer survivors [37,38].

Among survivors, we also observed a higher risk for CVD mortality. Several pathways might explain these associations. For example, smoking activates several CVD-relevant inflammatory markers, which lead to a significant shift toward a prothrombotic, procoagulative state, and release of pro-oxidant enzymes in the vascular wall by activating the nuclear factor-kB cascade [39]. The increase in reactive oxygen species and oxidant-generating systems induced by smoking leads to both systemic and local immune system activation [40,41]. Systemic inflammation is supported by upregulating the expression of various matrix metalloproteinases and proinflammatory cytokines among smokers. Tumor necrosis factor-α and interleukin-1β maintain sustained activation of nuclear factor-kB, perpetuating the inflammatory response in smokers [42]. Besides, nicotine also stimulates growth of advanced atherosclerotic lesions by increasing lesion vascularization [43] and smoking and/or nicotine might also accelerate atherosclerosis in other ways [44].

Limitations

Our study’s strengths include a prospective design, a large number of cancer cases and examining the associations between active smoking and risk of all-cause and disease-specific mortality. Information on smoking and other essential covariates was prospectively collected and updated periodically. However, there were several limitations. Firstly, smoking status was self-reported and assessed post-diagnosis, which may limit the risk difference comparison between pre-diagnosis and post-diagnosis smoking as well as be subject to recall and reporting biases. In addition, because of the nature of an observational study, causality cannot be established. Given that we have no information on passive smoking among non-smokers, the present risk estimate for the association between smoking and mortality may have been underestimated.

Implications for clinicians

The prevalence of smoking among cancer patients is still higher than expected since [45] smoking is detrimental to cancer therapy and survival [31,32,34-37]. Our data provides compelling evidence that smoking increases the risk of all-cause and cause-specific mortality among cancer survivors. Thus clinicians should provide survivors with care guidelines that promote smoking cessation as a crucial strategy for improving survival outcomes, especially since quit time was associated with mortality. The association between smoking and CVD mortality risk in select groups deserve further attention and has clinical implications for many as a reasonable proportion of survivors die of CVD. Thus, there is a need for strategies to manage CVD risk factors throughout the cancer continuum.

Conclusions

Post-diagnosis smoking was associated with increased all-cause, cancer and CVD mortality among cancer survivors, with varying associations depending on the survivor population. Dose-response associations of quit time for former smokers were obvious among all cancer survivors, especially in non-melanoma skin cancer survivors. Further research is needed to understand mechanisms whereby smoking may increase colorectal cancer-specific mortality and determine whether quit time after diagnosis lowers the risk of colorectal cancer-specific mortality.

Acknowledgements

We greatly appreciate the support from other members of the study team who provided their generous contribution of time and efforts help during the research and the help from Chengye Li for commenting on the manuscript. This study was not funded by any funding agencies in the public, commercial, or not-for-profit sectors. The study was funded by the National Natural Science Foundation of China (Grant No. 81773552) and the National Key Research and Development Program of China (No. 2018YFC1315302, 2017YFC1200502).

Disclosure of conflict of interest

None.

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