Association of healthy lifestyle score with all-cause mortality and life expectancy: a city-wide prospective cohort study of cancer survivors

China has about one fifth of global cancer cases [1, 2]. Although cancer survival has overall increased during the past decades [3], people with cancer had a shorter life expectancy than their peers without the disease [4], ranging from 2.4 to 11.2 years, depending on methods and study populations [4, 5]. Efforts to reduce morbidity and mortality of cancer, such as adherence to a healthy lifestyle, have been advocated in the general population based on published studies [6‐9]. For example, previous studies showed that four major unhealthy lifestyle factors (i.e., cigarette smoking, heavy alcohol use, lack of physical activity, and unhealthy diet) contributed to at least 60% of premature deaths, leading to a loss of 7.4–17.9 years in life expectancy [6, 10‐12]. However, in cancer survivors, whether adopting a healthy lifestyle will also have similar beneficial effects on life expectancy is unclear.

Hence, our study hereby explored the associations of the individual and combined healthy lifestyle factors with the risk of mortality in cancer survivors, and estimated the association of adherence to healthy lifestyles with life expectancy. Results of this study will facilitate evidence-based tertiary preventive strategies for providing holistic care and improving the quality of life in cancer survivors [13, 14].

Of 47,470 survivors recruited from 2010 to 2017, after excluding those with aged <18 years (n = 141) and those with missing information on sex (n = 2), age (n = 85), BMI (n = 1,192), smoking status (n = 2), and alcohol use (n = 2) at baseline, a total of 46,120 cancer survivors (21,071 men and 25,049 women) were included. The sample selection process was shown in the Additional file 1: Figure S1.

Of 46,120 cancer survivors, 34.8%, 47.0%, 13.2%, and 5.0% had a healthy lifestyle score of 5, 4, 3, and 0–2, respectively. Table 1 shows that participants with healthy lifestyle score of 5 were older; had more women; tended to be unemployed; have undergone surgery, chemotherapy, and radiation therap;, and had higher BMI and education. They also tended to be never smokers and non-alcohol users, be more physically active, and had longer duration of sleep. Similar patterns were found in survivors of different cancer types (Additional file 2: Tables S1 to S7). Additional file 2: Table S8 shows that most cancer survivors were tended to be never smoking had limited alcohol use, regular physical activity, and sufficient sleeping duration. During an average follow-up of 4.3 years (standard deviation= 2.3 years; 204,833 person-years), 15,707 deaths were recorded.

Additional file 2: Tables S9 shows that all lifestyle factors were associated with the risk of all-cause mortality. In multivariable Cox regression models, normal (18.5–23.9 kg/m²) or high (≥ 24.0 kg/m²) BMI, higher physical activity (≥ 2 h/week), and sleep duration (≥ 6 h/day) were significantly associated with a lower risk of mortality in cancer survivors. Compared with never smoking, former and current smoking were significantly associated with a higher risk of mortality (HR 1.83, 95% CI 1.73 to 1.93, and HR 1.67, 95% CI 1.58 to 1.77, respectively). Alcohol users also showed a significantly higher risk of all-cause mortality (HR 1.09, 95% CI 1.03 to 1.16). When stratifying by types of cancer, normal to high BMI, higher physical activity, and sufficient sleep duration were significantly associated with a lower risk of death in survivors of most cancer types (breast cancer, colorectal cancer, lung cancer, liver cancer, nasopharynx cancer, and gastric cancer) (Additional file 2: Tables S10–S15), and current smoking was associated with a higher risk of death in colorectal cancer survivors. Normal to high BMI and higher physical activity were significantly associated with a lower risk of death in kidney cancer (Additional file 2: Table S16).

For all cancer survivors, the associations with risk of mortality were more pronounced in women than men (Additional file 3: Figure S2B). Compared with the healthy lifestyle score of 5, female and male survivors with a score of 0–2 had a higher risk of mortality, with the adjusted HR (95% CI) being 2.59 (2.03, 3.30) and 1.91 (1.77, 2.05), respectively. We also found that the associations varied by age groups (Additional file 3: Figure S2C), with the adjusted HR (95% CI) for a score of 0–2 being 2.28 (2.03, 2.55) in younger (< 65 years) and 1.90 (1.75, 2.05) in older (≥ 65 years) group (Table 2).

Similar findings were found when stratifying by types of cancer. However, for survivors of most cancer types except breast cancer, colorectal cancer, and nasopharynx cancer, mortality risk was more pronounced in men (Additional file 2: Tables S17-S23). We also found that the associations were more pronounced in younger age groups in survivors of breast, liver, nasopharynx, gastric, and kidney cancer, but not varied by sex in colorectal cancer and lung cancer survivors (Additional file 4: Figure S3A-S3U).

Figure 1 shows that, for those with a score of 0–2, 3, 4, and 5, the life expectancy at age 55 was 53.4, 55.2, 56.1, and 57.1 months, respectively. Sensitivity analyses using leave-one-out showed similar results (Fig. 2a–e). Moreover, Fig. 3 shows that cancer survivors with a score of 5 had a life expectancy of 59.9 (95% CI 59.5 to 60.3) months on average, which was substantially longer than those with a score of 0–2 (46.2 months on average, 95% CI 45.3 to 47.1). The positive associations between scores and life expectancy were consistent across different age groups (Fig. 3).

Figures 4 shows the life expectancy by each lifestyle factor. Never smoking (Fig. 4a), never alcohol use (Fig. 4b), higher levels of physical activity (Fig. 4c), sufficient sleep duration (Fig. 4d), and normal BMI (Fig. 4e) were associated with a longer life expectancy. In addition, we found that cancer survivors with alcohol use and smoking had a shorter life expectancy. The average life expectancy in smokers was 47.7 months (95% CI: 47.5 to 47.9), which was lower than never smokers (55.6 months, 95% CI: 55.4 to 55.9) (Fig. 4a). Similar patterns were found for alcohol use, with the average life expectancy being 47.4 (95% CI 46.5 to 48.3) months for alcohol users and 54.9 (95% CI 54.7 to 55.2) months for never alcohol users (Fig. 4b).

In this study of near fifth thousand cancer survivors in China, all defined healthy lifestyle factors were independently associated with a lower risk of all-cause mortality. Survivors with cancer or different types of cancer who adopted healthy lifestyle behaviors had significantly lower risks of death. Furthermore, our results also indicate that cancer survivors can gain an average of about 4 months life expectancy at age 55 by adopting a healthy lifestyle, which should be important in primary care settings to promote healthy lifestyles.

Our results are generally consistent with previous studies from the western settings [7, 8, 31, 32]. Although lifestyle factors included in each study were slightly different, results of all studies consistently showed beneficial effects on all-cause mortality by adopting healthy lifestyles. The Nurses’ Health Study (NHS) and Health Professions Follow-up Study (HPFS) showed that adherence to never smoking, regular physical activity and healthy diet, and maintenance of a normal weight were associated with a lower risk of cancer mortality and a longer life expectancy [7, 8]. A large study in Europe found that of participants without chronic diseases (cardiovascular disease, cancer, respiratory disease, and diabetes), those with at least 2 high-risk factors (smoking, physical inactivity, and obesity) had a shorter life expectancy by 6 years compared to those without any of these three risk factors [31]. In the EPIC-Heidelberg cohort in Germany, healthy lifestyles (i.e., no smoking, healthier BMI, no-to-low alcohol use, and low processed/red meat consumption) were associated with a longer life expectancy by 17.0 years in men and 13.9 years in women at age 40 [32]. Furthermore, the Singapore Chinese Health Study also found that adherence to 4–5 healthy lifestyle factors, relative to those without any healthy lifestyle factors, showed a longer life expectancy by 8.1 years in women and 6.6 years in men at age 50 [9]. All the studies above were conducted in the general populations. However, evidence concerning the association of adopting healthy lifestyles with the risk of mortality and life expectancy in cancer survivors were scarce. Our results for the first time showed that even in cancer survivors, adherence to healthier lifestyle behaviors still exerts beneficial effects and needs to be encouraged. Hence, our results may provide important supplementary evidence to be used in clinical practice.

Previous studies showed that overweight and obesity were associated with a higher risk of cancer in the general population [33]. However, our study found that higher BMI was a protective factor in cancer survivors. Recent studies showed that cancer patients with lower BMI had a higher risk of mortality than patients with obesity [34, 35]. A review also showed that obesity was associated with a lower risk of mortality in cancer patients, suggesting an existence of ‘obesity paradox’ [36]. However, as most of the cancer survivors in our study had a normal BMI (18.5–23.9kg/m²), whether obesity plays a role in the prognosis of cancer survivors warrants further investigation. Moreover, it is worth mentioning that light-to-moderate alcohol consumption was shown as protective in the general population [7‐9]. We found that alcohol use was not associated with mortality risk in colorectal cancer survivors, which was consistent with a previous meta-analysis [37]. However, our study found that alcohol use was significantly associated with higher risk of all-cause mortality and lower life expectancy in cancer survivors. Hence, our results support that there is no safe limit for alcohol intake in most cancer survivors [38].

Our study has some strengths and limitations. Strengthens of our study include its longitudinal study design, large sample size, and city-wide representative sample of cancer survivors. There are also some limitations to be considered and discussed. First, information of the lifestyle factors was collected via self-reports using simple questions. Thus, details of each lifestyle factors, such as types of alcohol used and physical activity were not assessed. However, using simple questions might reduce misclassification of exposures and could facilitate further public health information translation. Second, lifestyle factors were measured at baseline and some factors might have changed during the follow-up, which, if any, tends to bias the results towards the null. Third, as other traditional observational cohort studies, residual confounding due to unmeasured or unknown factors could not be ruled out. Fourth, as most cancer epidemiologic studies, information of stages of cancer and duration from disease onset to diagnosis was unavailable. Fifth, as all cancer patients were from Guangzhou, China, our results might not be directly applicable to other settings or ethnicities. Finally, we did not include diet in the lifestyle score. However, because dietary patterns varied greatly across settings, and there is no consensus on the definition of a healthy diet pattern in cancer survivors [7, 8], further studies exploring healthy dietary patterns in site specific cancer survivors are also needed.

In summary, adopting a healthy lifestyle was associated with a substantially lower risk of all-cause mortality and longer life expectancy in cancer survivors. Our findings should be useful for health education and health promotion in primary care and clinical practice.