Background: Smoking and drinking alcohol are major risk factors for cancer development, and we investigated their effects on gastric cancer prognosis following initial resection.

Methods: Data from male patients with stage III–IV gastric adenocarcinoma who underwent surgery between 2001 and 2006 were retrospectively reviewed. Patients were followed up until 2011. Kaplan–Meier plots and Cox proportional hazards regressions were applied for survival rates.

Results: Among 238 patients, 151 (63.4%) smoked and 146 (61.3%) drank alcohol. Current smokers had an increased risk of cancer recurrence or death from any cause [adjusted HR (aHR), 1.94; 95% confidence interval (CI), 1.18–3.21], cancer recurrence (aHR, 1.89; 95% CI, 1.12–3.21), and overall mortality (aHR, 2.14; 95% CI, 1.23–3.73) compared with never-smokers. Patients with a lifetime cigarette smoking of <40 and ≥40 pack-years had increased cancer recurrence or death from any cause (aHR, 1.72 and 2.43, respectively; 95% CI, 1.03–2.86 and 1.38–4.30, respectively), cancer recurrence (aHR, 1.63 and 2.61, respectively; 95% CI, 0.95–2.79 and 1.43–4.77, respectively), and overall mortality (aHR, 1.92 and 2.75, respectively; 95% CI, 1.09–3.38 and 1.47–5.12, respectively) compared with never-smokers. However, drinking alcohol was not associated with postsurgery survival.

Conclusions: Cigarette-smoking history at the time of diagnosis, but not drinking history, is associated with cancer recurrence and poor survival after surgery in male patients with stage III–IV gastric cancer.

Impact: These findings encourage physicians to advise patients with gastric cancer to stop smoking to obtain a general health benefit and likely improvement in the gastric cancer course. Cancer Epidemiol Biomarkers Prev; 22(10); 1805–12. ©2013 AACR.

In Republic of Korea, the overall age-standardized gastric cancer incidence rate in 2009 was 43.0 per 100,000 persons (64.5 and 25.5 in males and females, respectively), and gastric cancer was the second most common cancer in the total population and the most common cancer in males (1). Gastric cancer survival rates have been increasing steadily due to better detection methods and more effective adjuvant therapies (1–3). Recently, the effects of modifiable risk factors such as smoking and alcohol drinking on cancer patient survival were studied as part of an effort to improve survival. Smoking was associated with poor prognosis in patients with lung (4), liver (5), colon (6, 7), and prostate cancer (8), and in non-Hodgkin lymphoma (NHL; ref. 9). Heavy drinkers had worse outcomes for head, neck, liver (5), and breast cancer (10), and NHL (9), in a dose-dependent manner.

Although smoking and alcohol drinking are well-known preventable risk factors for developing gastric cancer (11–15), the precise impact of smoking and alcohol drinking history on gastric cancer survival rates remained controversial. In a Japanese study with 877 patients with gastric cancer, the risk ratio for death was 2.53 [95% confidence interval (CI), 1.22–5.29] for habitual smokers, and an inverse dose–response relationship was found between ever smoking and gastric cancer patient survival (16). On the other hand, in a study with 14,578 Korean men, Park and colleagues identified that patients with gastric cancer with a prediagnosis smoking history had better survival rates than nonsmokers in multivariate-adjusted analyses (HR for mortality, 0.83; 95% CI, 0.72–0.95; ref. 5). Alcohol intake was also associated with an excess risk of dying, and a dose–response relationship with increasing levels of consumption was shown (Ptrend = 0.02). Patients in the highest tertile of alcohol intake had a 40% increased risk of all-cause death (HR, 1.41; 95% CI, 1.04–1.91; ref. 17). However, in a Japanese study, current or ever-habitual drinking did not significantly increase mortality HRs (16).

Because the effect of smoking and alcohol drinking on the survival of patients with gastric cancer remained unclear, we carried out a study to evaluate the effect of these factors on the prognoses of patients with gastric cancer in a Korean population.

Study population

In this retrospective study, patients presenting to the Center for Gastric Cancer at the National Cancer Center (NCC), a tertiary referral cancer center hospital, in Goyang, Republic of Korea between August 2001 and June 2006 were potentially eligible for inclusion. Male patients were included if they: (i) were of ages 20 years or older, (ii) had a histologically confirmed stage III/IV gastric adenocarcinoma, (iii) had newly diagnosed cancer without previous treatment, (iv) underwent R0 total or subtotal gastrectomy, and (v) completed an interview about health behavior (smoking and alcohol drinking history and current status). Finally, our study included 238 male patients. Only patients with stage III–IV gastric cancer were analyzed because the survival of patients with cancer differs substantially between stages (18). This study was approved by the Institutional Review Board of the NCC in Republic of Korea (NCCNCS-13-721).

The majority of patients with stage III–IV cancer with lymph node metastasis received adjuvant chemotherapy. Several combination chemotherapies were administered every 3 weeks for six to eight cycles. The detailed information about the chemotherapy regimen used is described elsewhere (19).

Clinical data

Clinical data were obtained from a review of medical records at the NCC. Clinicopathologic characteristics included tumor location, tumor size, Lauren classification, depth of invasion, lymph node metastasis, adjuvant chemotherapy, operation method, lymph node dissection, tumor stage, and first-degree family history of gastric cancer. The stage at diagnosis was determined with adherence to the sixth edition of the Union for International Cancer Control/American Joint Committee on Cancer classification system (20). Family history of cancer was ascertained by self-reporting and positive first-degree relatives including siblings, parents, or offsprings with gastric cancer.

Smoking and alcohol consumption assessment

Smoking status, smoking duration, number of cigarettes smoked per day, and cumulative pack-years information was collected by self-reporting through an interview with the physicians at the time of cancer diagnosis. Smoking status was categorized as never-smoker, ex-smoker, or current smoker based on the smoking history that the patients reported at the time of cancer diagnosis. Smokers were defined as patients who had smoked at least 1 year in their lifetime. Ex-smokers were defined as patients who had stopped smoking at least 12 months before cancer diagnosis. Current smokers were patients who were smoking within 1 year before the diagnosis, regardless of their smoking status thereafter. So, those who had given up smoking more recently (less than 12 months prior) were considered as current smokers. From former smokers, data about age at first smoking, the time since smoking cessation, and the number of cigarettes previously smoked per day were collected. From current smokers, data about the age at first smoking and the number of cigarettes smoked per day were collected. Smoking duration was categorized as never-smoker, less than 30 years, and 30 or more years. The number of cigarettes smoked per day was categorized as never-smoker, 20 or less per day, and more than 20 per day. Lifetime pack-years were defined as the estimated number of packs of cigarettes smoked per year over the subject's lifetime. Pack-years were divided into three groups: never-smoker, <40 pack-years, and ≥40 pack-years.

Alcohol drinking status was categorized as never, ex-drinker, or current drinker. In ex-drinkers or current drinkers, alcohol drinking frequency (never, ≤3 times/week, 4–5 times/week, or every day), duration of alcohol drinking (never, <20, 20–39, and ≥40 years), and alcohol-consumption amount (never, <30 g/day, and ≥30 g/day) data were additionally collected. Alcohol-consumption amount was calculated as grams of pure alcohol, based on the beverage type (soju, beer, makgeolli, and spirits) and the amount of each type consumed on a typical drinking day, assuming the following alcohol content by volume: soju 25%, beer 4%, makgeolli 5%, and spirits 40%. Soju (distilled spirits) and makgeolli (unrefined rice wine) are traditional alcoholic beverages in Republic of Korea.

Statistical analysis

The main outcome was disease-free survival (DFS), which was defined as the time from surgery to tumor recurrence, occurrence of a new primary gastric cancer, or death from any cause. Recurrence-free survival (RFS) was defined as the time from surgery to tumor recurrence, death with evidence of recurrence, or occurrence of a new metachronous gastric tumor. Patients who died without confirmed tumor recurrence were censored at the last documented evaluation. Overall survival (OS) was defined as the time from surgery to death from any cause.

Follow-up data through June 2011 were obtained for recurrence or death. Survival curves were constructed using the Kaplan–Meier method, and a log-rank test was used for comparison. Multivariate analyses were conducted using the Cox proportional hazards model adjusting for age, smoking, drinking, tumor location, tumor size, Lauren classification, adjuvant chemotherapy, tumor stage, and first-degree family history of gastric cancer for DFS, RFS, and OS. All analyses were conducted using SAS software (version 9.1; SAS Institute).

Among the 478 patients with stage III–IV gastric cancer who underwent total or subtotal gastrectomy from 2001 to 2006, all 150 female patients were excluded. Furthermore, 90 male patients were excluded because of missing values in smoking or alcohol drinking status. Finally, 238 men were included in this study and their mean age was 56.0 ± 11.8 years. More than 77% of the tumors were located in the lower two third of the stomach. The mean tumor diameter was 6.7 ± 2.8 cm and 18.9% patients had a first-degree family history of gastric cancer (Table 1).

Table 1.

Baseline characteristics of the study population

N = 238
Age, y 
 ≤49 76 (31.9) 
 50–59 65 (27.3) 
 60–69 60 (25.2) 
 ≥70 37 (15.6) 
 Overall mean patient age ± SD, y 56.0 ± 11.82 
Location of tumor 
 Upper one third 46 (19.3) 
 Lower two third 185 (77.7) 
 Whole stomach 7 (2.9) 
Tumor diameter, cm 
 <4.0 29 (12.2) 
 4.0–5.9 71 (29.8) 
 ≥6.0 138 (58.0) 
 Overall mean tumor diameter ± SD 6.7 ± 2.80 
Lauren classification 
 Intestinal 121 (50.8) 
 Diffuse or mixed type 117 (49.2) 
Depth of invasiona 
 ≤pT2 68 (28.6) 
 pT3 112 (47.1) 
 pT4 58 (24.4) 
LN metastasisa 
 ≤N1 63 (26.5) 
 N2 154 (64.7) 
 N3 21 (8.8) 
Adjuvant chemotherapy 
 No 31 (13.0) 
 Yes 207 (87.0) 
Operation method 
 Subtotal gastrectomy 131 (55.0) 
 Total gastrectomy 107 (45.0) 
LN dissection 
 D1 2 (0.8) 
 D2 236 (99.2) 
Tumor stagea 
 III 170 (71.4) 
 IV 68 (28.6) 
First-degree family history of gastric cancer 
 No 193 (81.1) 
 Yes 45 (18.9) 
N = 238
Age, y 
 ≤49 76 (31.9) 
 50–59 65 (27.3) 
 60–69 60 (25.2) 
 ≥70 37 (15.6) 
 Overall mean patient age ± SD, y 56.0 ± 11.82 
Location of tumor 
 Upper one third 46 (19.3) 
 Lower two third 185 (77.7) 
 Whole stomach 7 (2.9) 
Tumor diameter, cm 
 <4.0 29 (12.2) 
 4.0–5.9 71 (29.8) 
 ≥6.0 138 (58.0) 
 Overall mean tumor diameter ± SD 6.7 ± 2.80 
Lauren classification 
 Intestinal 121 (50.8) 
 Diffuse or mixed type 117 (49.2) 
Depth of invasiona 
 ≤pT2 68 (28.6) 
 pT3 112 (47.1) 
 pT4 58 (24.4) 
LN metastasisa 
 ≤N1 63 (26.5) 
 N2 154 (64.7) 
 N3 21 (8.8) 
Adjuvant chemotherapy 
 No 31 (13.0) 
 Yes 207 (87.0) 
Operation method 
 Subtotal gastrectomy 131 (55.0) 
 Total gastrectomy 107 (45.0) 
LN dissection 
 D1 2 (0.8) 
 D2 236 (99.2) 
Tumor stagea 
 III 170 (71.4) 
 IV 68 (28.6) 
First-degree family history of gastric cancer 
 No 193 (81.1) 
 Yes 45 (18.9) 

NOTE: Data are expressed as number (%).

aUnion for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system, sixth edition.

Abbreviation: LN, lymph node.

Smoking and alcohol consumption behavior

Among 238 male patients with gastric cancer, 18.5% and 63.4% were ex- and current smokers, respectively. Approximately, 39% of patients smoked for 30 years or more and 15.5% of patients smoked more than 20 cigarettes (one pack) per day. Furthermore, 58.8% and 23.1% of the patients had less than and more than 40 pack-years, respectively (Table 2).

Table 2.

Distribution of cigarette smoking and alcohol-drinking behavior

N = 238
Cigarette-smoking status 
 Never-smoker 43 (18.1) 
 Ex-smoker 44 (18.5) 
 Current smoker 151 (63.4) 
Smoking duration, y 
 Never-smoker 43 (18.1) 
 <30 103 (43.3) 
 ≥30 92 (38.7) 
Number of cigarettes smoked per day 
 Never-smoker 43 (18.1) 
 ≤20 158 (66.4) 
 >20 37 (15.5) 
Lifetime cigarette smoking (pack-years) 
 Never-smoker 43 (18.1) 
 <40 140 (58.8) 
 ≥40 55 (23.1) 
Alcohol-drinking status 
 Never drank 52 (21.8) 
 Ex-drinker 40 (16.8) 
 Current drinker 146 (61.3) 
Alcohol-drinking frequency, per weeka 
 Never drank 52 (22.0) 
 ≤3 112 (47.5) 
 4–5 32 (13.6) 
 Every day 40 (16.9) 
Duration of alcohol drinking, yb 
 Never drank 52 (22.3) 
 <20 29 (12.5) 
 20–39 90 (38.6) 
 ≥40 62 (26.6) 
Alcohol-consumption amount, g/da 
 Never drank 52 (22.0) 
 <30 88 (37.3) 
 ≥30 96 (40.7) 
N = 238
Cigarette-smoking status 
 Never-smoker 43 (18.1) 
 Ex-smoker 44 (18.5) 
 Current smoker 151 (63.4) 
Smoking duration, y 
 Never-smoker 43 (18.1) 
 <30 103 (43.3) 
 ≥30 92 (38.7) 
Number of cigarettes smoked per day 
 Never-smoker 43 (18.1) 
 ≤20 158 (66.4) 
 >20 37 (15.5) 
Lifetime cigarette smoking (pack-years) 
 Never-smoker 43 (18.1) 
 <40 140 (58.8) 
 ≥40 55 (23.1) 
Alcohol-drinking status 
 Never drank 52 (21.8) 
 Ex-drinker 40 (16.8) 
 Current drinker 146 (61.3) 
Alcohol-drinking frequency, per weeka 
 Never drank 52 (22.0) 
 ≤3 112 (47.5) 
 4–5 32 (13.6) 
 Every day 40 (16.9) 
Duration of alcohol drinking, yb 
 Never drank 52 (22.3) 
 <20 29 (12.5) 
 20–39 90 (38.6) 
 ≥40 62 (26.6) 
Alcohol-consumption amount, g/da 
 Never drank 52 (22.0) 
 <30 88 (37.3) 
 ≥30 96 (40.7) 

NOTE: Data are expressed as number (%).

aExcluded two cases whose alcohol-drinking frequency and amount were not obtained.

bExcluded five cases whose alcohol-drinking duration was not obtained.

With regard to alcohol-drinking behavior, 16.8% and 61.3% of patients were ex- and current drinkers, respectively. Approximately, 16.9% of patients drank every day and 26.6% drank for more than 40 years. Furthermore, 40.7% drank more than 30 g alcohol per day (Table 2).

Effect of smoking and alcohol drinking on the survival of stage III–IV gastric cancer patients

The overall DFS, RFS, and OS at 5 years were 43.2%, 47.6%, and 51.3%, respectively. In the Kaplan–Meier survival curves, DFS at 5 years of never-, ex-, and current smokers were 58.1%, 37.2%, and 40.7%, respectively (P = 0.080; Fig. 1). According to the lifetime amount of cigarette smoking, DFS was significantly better in patients who had never smoked compared with smokers with 40 pack-years or more (P = 0.008; Fig. 2). DFS at 5 years was 58.1% for never-smokers compared with 44.6% and 27.7% for smokers with less than 40 pack-years and smokers with 40 pack-years or more, respectively (overall P = 0.008, Ptrend = 0.002; Fig. 2).

Figure 1.

DFS curves of patients after gastric cancer resection according to cigarette-smoking status. Overall comparison P = 0.080. Never-smokers versus ex-smokers, P = 0.192. Never-smokers versus current smokers, P = 0.134. Ex-smokers versus current smokers, P = 0.807.

Figure 1.

DFS curves of patients after gastric cancer resection according to cigarette-smoking status. Overall comparison P = 0.080. Never-smokers versus ex-smokers, P = 0.192. Never-smokers versus current smokers, P = 0.134. Ex-smokers versus current smokers, P = 0.807.

Close modal
Figure 2.

DFS curves of patients after gastric cancer resection according to lifetime cigarette smoking (pack-years). Overall comparison P = 0.008 (Ptrend = 0.002). Never-smokers versus less than 40 pack-years, P = 0.627. Never-smokers versus 40 pack-years or more, P = 0.008. Less than 40 pack-years versus 40 years or more, P = 0.324.

Figure 2.

DFS curves of patients after gastric cancer resection according to lifetime cigarette smoking (pack-years). Overall comparison P = 0.008 (Ptrend = 0.002). Never-smokers versus less than 40 pack-years, P = 0.627. Never-smokers versus 40 pack-years or more, P = 0.008. Less than 40 pack-years versus 40 years or more, P = 0.324.

Close modal

The Cox proportional hazard model showed significant associations between cigarette smoking and survival in male patients with stage III–IV gastric cancer. Current smokers had an increased risk of cancer recurrence or death from any cause [adjusted HR (aHR), 1.94; 95% CI, 1.18–3.21], cancer recurrence (aHR, 1.89; 95% CI, 1.12–3.21), and overall mortality (aHR, 2.14; 95% CI, 1.23–3.73) compared with never-smokers after controlling for patient age, alcohol drinking status, tumor location, tumor size, Lauren classification, adjuvant chemotherapy, tumor stage, and first-degree family history of gastric cancer. Also, lifetime cigarette smoking (pack-years) of less than 40 and 40 years or more had increased cancer recurrence or death from any cause (aHR, 1.72 and 2.43, respectively; 95% CI, 1.03–2.86 and 1.38–4.30, respectively), cancer recurrence (aHR, 1.63 and 2.61, respectively; 95% CI, 0.95–2.79 and 1.43–4.77, respectively), and overall mortality (aHR, 1.92 and 2.75, respectively; 95% CI, 1.09–3.38 and 1.47–5.12, respectively) compared with never-smokers. Smokers who had a longer duration of smoking and greater numbers of cigarette smoking per day showed significantly worse survival (Table 3). However, alcohol-drinking status, alcohol-drinking frequency, duration of alcohol drinking, and alcohol-consumption amount in male patients with gastric cancer were not associated with survival (Table 4).

Table 3.

HRs for death and recurrence for stage III–IV male gastric cancer patients according to the cigarette-smoking behavior

Cancer recurrence or death from any causeCancer recurrenceOverall mortality
cHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)a
Cigarette-smoking status 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 Ex-smoker 1.73 (0.96–3.12) 1.74 (0.94–3.23) 1.70 (0.91–3.16) 1.78 (0.93–3.42) 2.11 (1.12–4.00) 2.13 (1.09–4.17) 
 Current smoker 1.73 (1.06–2.83) 1.94 (1.18–3.21) 1.72 (1.02–2.89) 1.89 (1.12–3.21) 1.89 (1.09–3.27) 2.14 (1.23–3.73) 
Smoking duration, y 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 <30 1.59 (0.95–2.67) 1.64 (0.96–2.81) 1.63 (0.95–2.81) 1.64 (0.93–2.88) 1.78 (1.01–3.15) 1.87 (1.03–3.39) 
 ≥30 1.89 (1.13–3.16) 2.25 (1.31–3.88) 1.81 (1.05–3.13) 2.20 (1.23–3.93) 2.11 (1.19–3.73) 2.45 (1.36–4.44) 
Ptrend 0.017 0.003 0.043 0.008 0.012 0.003 
Number of cigarettes smoked per day 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 ≤20 1.63 (0.99–2.67) 1.79 (1.08–2.95) 1.62 (0.96–2.73) 1.73 (1.02–2.95) 1.77 (1.02–3.07) 1.96 (1.12–3.42) 
 >20 2.20 (1.22–3.97) 2.49 (1.36–4.55) 2.16 (1.16–4.03) 2.56 (1.36–4.84) 2.73 (1.45–5.13) 3.02 (1.58–5.79) 
Ptrend 0.008 0.003 0.014 0.003 0.001 0.001 
Lifetime cigarette smoking (pack-years) 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 <40 1.54 (0.94–2.55) 1.72 (1.03–2.86) 1.52 (0.90–2.58) 1.63 (0.95–2.79) 1.71 (0.98–2.97) 1.92 (1.09–3.38) 
 ≥40 2.29 (1.33–3.96) 2.43 (1.38–4.30) 2.29 (1.29–4.08) 2.61 (1.43–4.77) 2.63 (1.44–4.78) 2.75 (1.47–5.12) 
Ptrend 0.002 0.002 0.004 0.002 0.001 0.001 
Cancer recurrence or death from any causeCancer recurrenceOverall mortality
cHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)a
Cigarette-smoking status 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 Ex-smoker 1.73 (0.96–3.12) 1.74 (0.94–3.23) 1.70 (0.91–3.16) 1.78 (0.93–3.42) 2.11 (1.12–4.00) 2.13 (1.09–4.17) 
 Current smoker 1.73 (1.06–2.83) 1.94 (1.18–3.21) 1.72 (1.02–2.89) 1.89 (1.12–3.21) 1.89 (1.09–3.27) 2.14 (1.23–3.73) 
Smoking duration, y 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 <30 1.59 (0.95–2.67) 1.64 (0.96–2.81) 1.63 (0.95–2.81) 1.64 (0.93–2.88) 1.78 (1.01–3.15) 1.87 (1.03–3.39) 
 ≥30 1.89 (1.13–3.16) 2.25 (1.31–3.88) 1.81 (1.05–3.13) 2.20 (1.23–3.93) 2.11 (1.19–3.73) 2.45 (1.36–4.44) 
Ptrend 0.017 0.003 0.043 0.008 0.012 0.003 
Number of cigarettes smoked per day 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 ≤20 1.63 (0.99–2.67) 1.79 (1.08–2.95) 1.62 (0.96–2.73) 1.73 (1.02–2.95) 1.77 (1.02–3.07) 1.96 (1.12–3.42) 
 >20 2.20 (1.22–3.97) 2.49 (1.36–4.55) 2.16 (1.16–4.03) 2.56 (1.36–4.84) 2.73 (1.45–5.13) 3.02 (1.58–5.79) 
Ptrend 0.008 0.003 0.014 0.003 0.001 0.001 
Lifetime cigarette smoking (pack-years) 
 Never-smoker 1.00 1.00 1.00 1.00 1.00 1.00 
 <40 1.54 (0.94–2.55) 1.72 (1.03–2.86) 1.52 (0.90–2.58) 1.63 (0.95–2.79) 1.71 (0.98–2.97) 1.92 (1.09–3.38) 
 ≥40 2.29 (1.33–3.96) 2.43 (1.38–4.30) 2.29 (1.29–4.08) 2.61 (1.43–4.77) 2.63 (1.44–4.78) 2.75 (1.47–5.12) 
Ptrend 0.002 0.002 0.004 0.002 0.001 0.001 

aaHRs adjusted for age, alcohol drinking status, tumor location, tumor size, Lauren classification, adjuvant chemotherapy, tumor stage, and first-degree family history of gastric cancer.

Abbreviation: cHR, crude HR.

Table 4.

HRs for death and recurrence for stage III–IV male gastric cancer patients according to alcohol drinking behavior

Cancer recurrence or death from any causeCancer recurrenceOverall mortality
cHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)a
Alcohol-drinking status 
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 Ex-drinker 0.86 (0.49–1.50) 0.73 (0.41–1.30) 0.93 (0.52–1.65) 0.79 (0.43–1.45) 0.84 (0.47–1.50) 0.69 (0.38–1.26) 
 Current drinker 1.01 (0.67–1.53) 0.99 (0.66–1.51) 1.02 (0.66–1.59) 1.00 (0.64–1.57) 0.99 (0.65–1.53) 1.00 (0.65–1.55) 
Alcohol-drinking frequency (per weekb
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 ≤3 0.87 (0.56–1.33) 0.79 (0.51–1.22) 0.91 (0.58–1.43) 0.81 (0.51–1.29) 0.91 (0.58–1.41) 0.84 (0.53–1.33) 
 4–5 1.49 (0.87–2.54) 1.40 (0.81–2.42) 1.55 (0.88–2.74) 1.48 (0.83–2.63) 1.28 (0.74–2.24) 1.14 (0.65–2.01) 
 Every day 1.02 (0.60–1.73) 1.03 (0.59–1.78) 0.93 (0.52–1.66) 0.96 (0.53–1.75) 0.88 (0.50–1.56) 0.90 (0.49–1.65) 
Ptrend 0.459 0.366 0.690 0.479 0.974 0.874 
Duration of alcohol drinking, yc 
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 <20 0.81 (0.44–1.49) 0.72 (0.37–1.37) 0.80 (0.42–1.53) 0.63 (0.32–1.26) 0.95 (0.51–1.75) 0.86 (0.45–1.65) 
 20–39 0.97 (0.63–1.50) 1.03 (0.65–1.63) 1.02 (0.65–1.60) 1.01 (0.62–1.64) 0.84 (0.54–1.32) 0.89 (0.55–1.44) 
 ≥40 1.11 (0.70–1.77) 0.94 (0.55–1.59) 1.07 (0.65–1.76) 1.02 (0.58–1.81) 1.13 (0.70–1.83) 0.91 (0.52–1.58) 
Ptrend 0.600 0.964 0.649 0.707 0.760 0.755 
Alcohol consumption amount, g/db 
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 <30 0.91 (0.58–1.42) 0.83 (0.52–1.31) 0.96 (0.60–1.54) 0.86 (0.53–1.39) 0.93 (0.58–1.47) 0.86 (0.53–1.38) 
 ≥30 1.06 (0.69–1.64) 1.02 (0.66–1.58) 1.05 (0.66–1.66) 1.01 (0.63–1.62) 0.99 (0.63–1.56) 0.95 (0.60–1.51) 
Ptrend 0.693 0.743 0.802 0.772 0.965 0.995 
Cancer recurrence or death from any causeCancer recurrenceOverall mortality
cHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)acHR (95% CI)aHR (95% CI)a
Alcohol-drinking status 
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 Ex-drinker 0.86 (0.49–1.50) 0.73 (0.41–1.30) 0.93 (0.52–1.65) 0.79 (0.43–1.45) 0.84 (0.47–1.50) 0.69 (0.38–1.26) 
 Current drinker 1.01 (0.67–1.53) 0.99 (0.66–1.51) 1.02 (0.66–1.59) 1.00 (0.64–1.57) 0.99 (0.65–1.53) 1.00 (0.65–1.55) 
Alcohol-drinking frequency (per weekb
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 ≤3 0.87 (0.56–1.33) 0.79 (0.51–1.22) 0.91 (0.58–1.43) 0.81 (0.51–1.29) 0.91 (0.58–1.41) 0.84 (0.53–1.33) 
 4–5 1.49 (0.87–2.54) 1.40 (0.81–2.42) 1.55 (0.88–2.74) 1.48 (0.83–2.63) 1.28 (0.74–2.24) 1.14 (0.65–2.01) 
 Every day 1.02 (0.60–1.73) 1.03 (0.59–1.78) 0.93 (0.52–1.66) 0.96 (0.53–1.75) 0.88 (0.50–1.56) 0.90 (0.49–1.65) 
Ptrend 0.459 0.366 0.690 0.479 0.974 0.874 
Duration of alcohol drinking, yc 
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 <20 0.81 (0.44–1.49) 0.72 (0.37–1.37) 0.80 (0.42–1.53) 0.63 (0.32–1.26) 0.95 (0.51–1.75) 0.86 (0.45–1.65) 
 20–39 0.97 (0.63–1.50) 1.03 (0.65–1.63) 1.02 (0.65–1.60) 1.01 (0.62–1.64) 0.84 (0.54–1.32) 0.89 (0.55–1.44) 
 ≥40 1.11 (0.70–1.77) 0.94 (0.55–1.59) 1.07 (0.65–1.76) 1.02 (0.58–1.81) 1.13 (0.70–1.83) 0.91 (0.52–1.58) 
Ptrend 0.600 0.964 0.649 0.707 0.760 0.755 
Alcohol consumption amount, g/db 
 Never drank 1.00 1.00 1.00 1.00 1.00 1.00 
 <30 0.91 (0.58–1.42) 0.83 (0.52–1.31) 0.96 (0.60–1.54) 0.86 (0.53–1.39) 0.93 (0.58–1.47) 0.86 (0.53–1.38) 
 ≥30 1.06 (0.69–1.64) 1.02 (0.66–1.58) 1.05 (0.66–1.66) 1.01 (0.63–1.62) 0.99 (0.63–1.56) 0.95 (0.60–1.51) 
Ptrend 0.693 0.743 0.802 0.772 0.965 0.995 

aaHRs adjusted for age, cigarette smoking status, tumor location, tumor size, Lauren classification, adjuvant chemotherapy, tumor stage, and first-degree family history of gastric cancer.

bExcluded two cases whose alcohol-drinking frequency and consumption amount were not obtained.

cExcluded five cases whose alcohol-drinking duration was not obtained.

Abbreviation: cHR, crude HR.

By using a cohort of resected patients with gastric cancer, we evaluated the impact of smoking and alcohol drinking on gastric cancer recurrence and survival. Cigarette smoking was significantly associated with poor survival. Especially, the dose–response association was noted for lifetime pack-years consumed. In contrast, alcohol-drinking behavior was not associated with survival.

In our study subjects, ex- and current smoking rates were 18.5% and 63.4%, respectively. The smoking rate in Korean adult males, which has been reported to be 48.3% in a 2010 survey, seems higher compared with that of other countries (21, 22). Our result was comparable with the previous Korean studies, showing a higher smoking rate in male patients with cancer than the general population. Ex- and current smokers constituted 17.2% and 64.8%, respectively, of the 14,578 Korean male patients with cancer in one study (5) and 17.2% and 56.7%, respectively, of the 12,242 male patients with gastric cancer in another study (15). Smoking is considered a main risk factor for gastric cancer in Republic of Korea. Men who smoked for 20 to 39 years had a 2.09-fold increased risk of gastric cancer compared with nonsmokers, and those who smoked for more than 40 years had a 3.13-fold increased risk (3).

In this study, the overall DFS, RFS, and OS at 5 years were 43.2%, 47.6%, and 51.3%, respectively. These figures are compatible but slightly higher than those reported in a recent Korean study (23). In agreement with our results, a Japanese study of gastric cancer (24) showed a better survival rate than that of Western studies (25, 26), despite an advanced stage. One of the main differences among the studies that can affect the outcome is the extent of lymph node dissection. The D2 dissection rate of both the Japanese and our study was more than 99% (24), whereas in the Western studies, the D2 dissection rate was only 10% in one study (25) and approximately 40% in another study (26). Also, surgical mortality might be low because the NCC in Korea is a high-volume center. Surgical patients in high-volume hospitals have shown significantly better survival than those in low- to medium-volume hospitals (27). Here, we included only patients who had R0 resection carried out. So, the survival rate of patients in our study was higher than that of overall stage III–IV patients.

Our observed lower survival rates in smokers compared with never-smokers might be due to the biologic effect of smoking and health behavior of smokers. Direct genotoxicity and nongenotoxic (epigenetic) effects of cigarette smoke underlie the mechanisms of tumor promotion and progression (28). Nicotine, although not carcinogenic by itself, has been shown to promote the growth of gastric cancer cells by stimulating cell proliferation and angiogenesis (29). Smokers have more rapidly progressing tumors and cancer metastasis than nonsmokers (28). Also, tobacco smoking has been shown to affect the immune system. Specifically, natural killer cell activity against cancer cells was reduced significantly in smokers (30).

The health behavior of smokers, which is not as good as that of never-smokers, may also contribute to this survival difference (31–34). In the 2006 Korean National Cancer Screening Survey, an annual cross-sectional survey that uses nationally representative random sampling to investigate the cancer-screening rates, current smokers showed lower rates of endoscopy use than nonsmokers (31). Hence, smokers may be at an increased risk of dying of gastric cancer or cancer recurrence due to the differences in the screening behavior rather than the smoking per se. In addition, other unhealthy lifestyles, such as low-fruit diet, inadequate physical activity, and unhealthy diet were risk factors for poor prognoses of gastric cancer (33, 34). These behaviors were observed more frequently in smokers versus nonsmokers (35, 36). The effect of screening participation and other health behavior could not be verified directly in our study because these data were not collected. Further studies are needed to clarify this point.

In this study, dose–response relationships were observed between postsurgery survival and lifetime cigarette smoking. Smokers who had longer pack-year accumulations showed significantly higher aHRs than never-smokers. Two earlier Asian studies showed the dose–response relationship between cigarette smoking and gastric cancer death. In a report studying Japanese men, daily cigarette consumption and mortality from gastric cancer showed a significant dose–response relationship (37). In a study from Taiwan, dose–response relationships between death from gastric cancer and the quantity of smoking, duration of smoking, age of smoking initiation, and cumulative cigarette smoking in pack-years were reported (38). However, these early reports did not control for other known clinicopathologic prognostic factors of gastric cancer. In our study, adjustment for known clinical factors associated with more aggressive tumor behavior did not fully attenuate our finding that greater smoking intensity equals lower survival after surgery.

Our observation of lack of a relationship between alcohol consumption and survival among patients with gastric cancer is consistent with several past studies (39, 40). In contrast, alcohol use was significantly associated with worse outcome among patients with stomach cancer in some studies (17, 41). These inconsistencies in the literature might be due to the way that the alcohol-drinking behavior is assessed, for example, in only assessing the alcohol-drinking status or the alcohol-consumption amount (17, 39, 42–44). In our study, alcohol consumption was assessed in terms of both alcohol-drinking status and amount. Therefore, the method of assessing alcohol drinking does not fully explain these inconsistencies.

There are some study limitations that should be considered. First, these analyses are based on the self-reporting of tobacco and alcohol-use history. Hence, the rates of reported smoking and alcohol consumption might have been underestimated as a result of social desirability. Previous study showed that 39.1% of ex-smokers who reported quit smoking within 1 year had an elevated serum cotinine level (45). Thus, the definition of current smokers in our study may reduce the risk of misrepresentation from the patients, but may also increase the risk of the people who were not actually using tobacco at the time of diagnosis. Second, we did not collect the information on changes in smoking and drinking habits subsequent to cancer diagnosis and surgery. Finally, only male patients with gastric cancer were analyzed, because we did not enroll enough women due to low smoking rate of women in Republic of Korea. In the Korea National Health and Nutrition Examination Survey 2010, the current smoking rate of women was 6.3% (21).

The strengths of the current study include the histologically confirmed incident gastric cancer cases and the detailed interview data that were assembled to evaluate the influence of risk factors on long-term survival. Compared with most previous studies, our study included information about cigarette-smoking volume and alcohol-consumption amount as well as cigarette-smoking status and alcohol-drinking status, which might more fully reflect smoking and alcohol abuse.

In summary, our study shows that the prognosis after surgical resection for stage III–IV gastric cancer is worse for smokers than never-smokers, particularly in current smokers. This finding warrants physicians to strongly advise patients with gastric cancer to stop smoking because of detrimental effects of current smoking on the course of their disease.

No potential conflicts of interest were disclosed.

Conception and design: M.A. Han, I.J. Choi, M.G. Oh

Development of methodology: M.A. Han, I.J. Choi

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): Y.-W. Kim, I.J. Choi, J.Y. Lee, B.W. Eom, H.M. Yoon, K.W. Ryu

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): M.A. Han, I.J. Choi, M.G. Oh

Writing, review, and/or revision of the manuscript: M.A. Han, Y.-W. Kim, M.G. Oh, C.G. Kim, S.-J. Cho

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): Y.-W. Kim

Study supervision: Y.-W. Kim, I.J. Choi

This work was supported by grant 1310280 from the National Cancer Center, Republic of Korea.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1.
Jung
KW
,
Park
S
,
Kong
HJ
,
Won
YJ
,
Lee
JY
,
Seo
HG
, et al
Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2009
.
Cancer Res Treat
2012
;
44
:
11
24
.
2.
Lee
JY
,
Jung
KW
,
Park
S
,
Kong
HJ
,
Won
YJ
,
Shin
HR
, et al
Long-term survival of cancer patients in Korea, 1993–2007: National Cancer Registry Study
.
Asian Pac J Cancer Prev
2010
;
11
:
1459
64
.
3.
Shin
A
,
Kim
J
,
Park
S
. 
Gastric cancer epidemiology in Korea
.
J Gastric Cancer
2011
;
11
:
135
40
.
4.
Parsons
A
,
Daley
A
,
Begh
R
,
Aveyard
P
. 
Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis
.
BMJ
2010
;
340
:
b5569
.
5.
Park
SM
,
Lim
MK
,
Shin
SA
,
Yun
YH
. 
Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: National Health Insurance Corporation Study
.
J Clin Oncol
2006
;
24
:
5017
24
.
6.
Phipps
AI
,
Baron
J
,
Newcomb
PA
. 
Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: the Seattle Colon Cancer Family Registry
.
Cancer
2011
;
117
:
4948
57
.
7.
McCleary
NJ
,
Niedzwiecki
D
,
Hollis
D
,
Saltz
LB
,
Schaefer
P
,
Whittom
R
, et al
Impact of smoking on patients with stage III colon cancer: results from CALGB 89809
.
Cancer
2010
;
116
:
957
66
.
8.
Kenfield
SA
,
Stampfer
MJ
,
Chan
JM
,
Giovannucci
E
. 
Smoking and prostate cancer survival and recurrence
.
JAMA
2011
;
305
:
2548
55
.
9.
Talamini
R
,
Polesel
J
,
Spina
M
,
Chimienti
E
,
Serraino
D
,
Zucchetto
A
, et al
The impact of tobacco smoking and alcohol drinking on survival of patients with non-Hodgkin lymphoma
.
Int J Cancer
2008
;
122
:
1624
9
.
10.
Kwan
ML
,
Kushi
LH
,
Weltzien
E
,
Tam
EK
,
Castillo
A
,
Sweeney
C
, et al
Alcohol consumption and breast cancer recurrence and survival among women with early-stage breast cancer: the life after cancer epidemiology study
.
J Clin Oncol
2010
;
28
:
4410
6
.
11.
Moy
KA
,
Fan
Y
,
Wang
R
,
Gao
YT
,
Mimi
CY
,
Yuan
JM
. 
Alcohol and tobacco use in relation to gastric cancer: a prospective study of men in Shanghai, China
.
Cancer Epidemiol Biomarkers Prev
2010
;
19
:
2287
97
.
12.
Sjödahl
K
,
Lu
Y
,
Nilsen
TIL
,
Ye
W
,
Hveem
K
,
Vatten
L
, et al
Smoking and alcohol drinking in relation to risk of gastric cancer: A population-based, prospective cohort study
.
Int J Cancer
2007
;
120
:
128
32
.
13.
Nishino
Y
,
Inoue
M
,
Tsuji
I
,
Wakai
K
,
Nagata
C
,
Mizoue
T
, et al
Tobacco smoking and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population
.
Jpn J Clin Oncol
2006
;
36
:
800
7
.
14.
Sasazuki
S
,
Sasaki
S
,
Tsugane
S
. 
Cigarette smoking, alcohol consumption and subsequent gastric cancer risk by subsite and histologic type
.
Int J Cancer
2002
;
101
:
560
6
.
15.
Sung
NY
,
Choi
KS
,
Park
EC
,
Park
K
,
Lee
SY
,
Lee
AK
, et al
Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study
.
Br J Cancer
2007
;
97
:
700
4
.
16.
Huang
XE
,
Tajima
K
,
Hamajima
N
,
Kodera
Y
,
Yamamura
Y
,
Xiang
J
, et al
Effects of dietary, drinking, and smoking habits on the prognosis of gastric cancer
.
Nutr Cancer
2000
;
38
:
30
6
.
17.
Palli
D
,
Russo
A
,
Saieva
C
,
Salvini
S
,
Amorosi
A
,
Decarli
A
. 
Dietary and familial determinants of 10‐year survival among patients with gastric carcinoma
.
Cancer
2000
;
89
:
1205
13
.
18.
Han
MA
,
Oh
MG
,
Choi
IJ
,
Park
SR
,
Ryu
KW
,
Nam
B-H
, et al
Association of family history with cancer recurrence and survival in patients with gastric cancer
.
J Clin Oncol
2012
;
30
:
701
8
.
19.
Eom
BW
,
Ryu
KW
,
Lee
JH
,
Choi
IJ
,
Kook
MC
,
Cho
SJ
, et al
Oncologic effectiveness of regular follow-up to detect recurrence after curative resection of gastric cancer
.
Ann Surg Oncol
2011
;
18
:
358
64
.
20.
Sobin
LH
,
Wittekind
C
. 
TNM classification of malignant tumours. 6th ed
.
New York
:
Wiley–Liss Inc
; 
2002
.
21.
Ministry of Health & Welfare; Korea Centers for Disease Control & Prevention. Korea Health Statistics 2010: Korea National Health and Nutrition Examination Survey (KNHANES V-1)
.
Seoul
:
Ministry of Health & Welfare
; 
2011
.
22.
Organization for Economic Cooperation Development
. 
Health at a glance 2011: OECD indicators
;
Paris, France
:
Organization for Economic Cooperation Development
; 
2011
.
23.
Ahn
HS
,
Lee
HJ
,
Hahn
S
,
Kim
WH
,
Lee
KU
,
Sano
T
, et al
Evaluation of the seventh American Joint Committee on Cancer/International Union against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification
.
Cancer
2010
;
116
:
5592
8
.
24.
Sakuramoto
S
,
Sasako
M
,
Yamaguchi
T
,
Kinoshita
T
,
Fujii
M
,
Nashimoto
A
, et al
Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine
.
N Engl J Med
2007
;
357
:
1810
20
.
25.
Macdonald
JS
,
Smalley
SR
,
Benedetti
J
,
Hundahl
SA
,
Estes
NC
,
Stemmermann
GN
, et al
Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction
.
N Engl J Med
2001
;
345
:
725
30
.
26.
Cunningham
D
,
Allum
WH
,
Stenning
SP
,
Thompson
JN
,
Van de Velde
CJ
,
Nicolson
M
, et al
Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer
.
N Engl J Med
2006
;
355
:
11
20
.
27.
Yun
YH
,
Kim
YA
,
Min
YH
,
Park
S
,
Won
YJ
,
Kim
DY
, et al
The influence of hospital volume and surgical treatment delay on long-term survival after cancer surgery
.
Ann Oncol
2012
;
23
:
2731
7
.
28.
Chen
RJ
,
Chang
LW
,
Lin
P
,
Wang
YJ
. 
Epigenetic effects and molecular mechanisms of tumorigenesis induced by cigarette smoke: an overview
.
J Oncol
2011
;
2011
:
654931
.
29.
Jensen
K
,
Afroze
S
,
Munshi
MK
,
Guerrier
M
,
Glaser
SS
. 
Mechanisms for nicotine in the development and progression of gastrointestinal cancers
.
Transl Gastrointest Cancer
2012
;
1
:
81
7
.
30.
Sopori
M
. 
Effects of cigarette smoke on the immune system
.
Nat Rev Immunol
2002
;
2
:
372
7
.
31.
Choi
KS
,
Kwak
MS
,
Lee
H
,
Jun
JK
,
Hahm
MI
,
Park
EC
. 
Screening for gastric cancer in Korea: population-based preferences for endoscopy versus upper gastrointestinal series
.
Cancer Epidemiol Biomarkers Prev
2009
;
18
:
1390
8
.
32.
Shin
JY
,
Lee
DH
. 
Factors associated with the use of gastric cancer screening services in Korea: the Fourth Korea National Health and Nutrition Examination Survey 2008 (KNHANES IV)
.
Asian Pac J Cancer Prev
2012
;
13
:
3773
9
.
33.
Doyle
C
,
Kushi
LH
,
Byers
T
,
Courneya
KS
,
Demark-Wahnefried
W
,
Grant
B
, et al
Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices
.
CA Cancer J Clin
2006
;
56
:
323
53
.
34.
Knols
R
,
Aaronson
NK
,
Uebelhart
D
,
Fransen
J
,
Aufdemkampe
G
. 
Physical exercise in cancer patients during and after medical treatment: a systematic review of randomized and controlled clinical trials
.
J Clin Oncol
2005
;
23
:
3830
42
.
35.
French
S
,
Rosenberg
M
,
Knuiman
M
. 
The clustering of health risk behaviours in a Western Australian adult population
.
Health Promot J Austr
2008
;
19
:
203
9
.
36.
Schneider
S
,
Huy
C
,
Schuessler
M
,
Diehl
K
,
Schwarz
S
. 
Optimising lifestyle interventions: identification of health behaviour patterns by cluster analysis in a German 50+ survey
.
Eur J Public Health
2009
;
19
:
271
7
.
37.
Akiba
S
,
Hirayama
T
. 
Cigarette smoking and cancer mortality risk in Japanese men and women–results from reanalysis of the six-prefecture cohort study data
.
Environ Health Perspect
1990
;
87
:
19
26
.
38.
Liaw
KM
,
Chen
CJ
. 
Mortality attributable to cigarette smoking in Taiwan: a 12-year follow-up study
.
Tob Control
1998
;
7
:
141
8
.
39.
Ferronha
I
,
Castro
C
,
Carreira
H
,
Bento
M
,
Carvalho
I
,
Peleteiro
B
, et al
Prediagnosis lifestyle exposures and survival of gastric cancer patients: a cohort study from Portugal
.
Br J Cancer
2012
;
107
:
537
43
.
40.
Shimazu
T
,
Tsuji
I
,
Inoue
M
,
Wakai
K
,
Nagata
C
,
Mizoue
T
, et al
Alcohol drinking and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population
.
Jpn J Clin Oncol
2008
;
38
:
8
25
.
41.
Ferronha
I
,
Bastos
A
,
Lunet
N
. 
Prediagnosis lifestyle exposures and survival of patients with gastric cancer: systematic review and meta-analysis
.
Eur J Cancer Prev
2012
;
21
:
449
52
.
42.
Yang
L
,
Zhou
M
,
Sherliker
P
,
Cai
Y
,
Peto
R
,
Wang
L
, et al
Alcohol drinking and overall and cause-specific mortality in China: nationally representative prospective study of 220 000 men with 15 years of follow-up
.
Int J Epidemiol
2012
;
41
:
1101
13
.
43.
Sundelöf
M
,
Lagergren
J
,
Ye
W
. 
Patient demographics and lifestyle factors influencing long-term survival of oesophageal cancer and gastric cardia cancer in a nationwide study in Sweden
.
Eur J Cancer
2008
;
44
:
1566
71
.
44.
Trivers
KF
,
de Roos
AJ
,
Gammon
MD
,
Vaughan
TL
,
Risch
HA
,
Olshan
AF
, et al
Demographic and lifestyle predictors of survival in patients with esophageal or gastric cancers
.
Clin Gastroenterol Hepatol
2005
;
3
:
225
30
.
45.
Khuri
FR
,
Kim
ES
,
Lee
JJ
,
Winn
RJ
,
Benner
SE
,
Lippman
SM
, et al
The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial
.
Cancer Epidemiol Biomarkers Prev
2001
;
10
:
823
9
.