Cumulative social risk exposure and risk of cancer mortality in adulthood

In the United States (U.S.) cancer accounts for 23 % of all deaths, and is the leading cause of death in adults aged 40 to 79 years [1]. However, cancer deaths are not uniformly distributed in the U.S. population with social disparities in cancer mortality being documented in the U.S. as far back as the early 20^th century [2]. As with studies on social disparities in health [3‐5], studies on social disparities and cancer mortality have mainly focused on single indicators of social disadvantage, such as low education [6‐8], low-income [6, 9, 10], minority race/ethnicity [8, 10, 11] and social isolation [12, 13].

But what happens when these social risk factors are experienced together? Socially disadvantaged adults may be exposed to multiple social risk factors simultaneously, with exposure occurring across time and domains [14]. Cumulative social risk exposure refers to experiencing more than one social risk factor at a time, and may better represent the complexity of social disadvantage compared to individual social risk factors [14, 15]. Given that these social risk factors can influence multiple health outcomes and operate via multiple and overlapping mechanisms [16], their co-occurrence as captured through an index of cumulative social risk may lead to larger health adversities, including mortality risk. We have previously shown that exposure to an increasing number of social risk factors were associated with a significantly increased risk of cardiovascular disease (CVD) mortality, premature mortality, and all-cause mortality in U.S. adults [17]. Extant research has not examined the cumulative effect of multiple social risk factors on cancer mortality. Using data from National Health and Nutrition Examination Survey (NHANES) III Mortality Study, a large US population-based cohort study, we created a cumulative risk score based on easily-measured social risk factors and examined the association between cumulative social risk and cancer mortality risk for all cancers combined. We also examined cumulative social risk in association to a combination of tobacco-related cancers, and a combination of screening-detectable cancers as mortality from these cancers represent potentially preventable causes of mortality, and prior research has shown that social disparities are larger for cancers for which there are known preventive risk factors, early detection and treatment methods [16, 18]. Because social risk factors may differentially affect mortality of each site-specific cancer, we also examined cumulative social risk in relation to mortality from the four most common cancer sites (excluding non-melanoma skin cancers) of breast, prostate, colon/rectum, and lung including trachea and bronchus [19].

The median duration of follow-up was 13.5 (range: 0.1-18.2) years. From 1988 to 2006, there were 3489 deaths (1813 in males and 1676 in females). Of these deaths, 699 deaths were from all-cancers combined (419 in males and 280 in females) 308 were from tobacco-related cancers (203 in males and 105 in females) and 166 from screening-detectable cancers (101 in males and 65 in females). The characteristics of participants are shown in Table 1. Compared to males, females were more likely to have low family income (8.7 % vs. 12.4 %; p < 0.001), belong to a minority race/ethnic group (18.9 % vs. 21.2 %; p = 0.009), live as a single person (21.4 % vs. 38 %; p = <0.001) and be exposed to ≥ 3 social risk factors (6.5 % vs. 10.0 %; p < 0.001). There was no evidence for interactions between each social risk factor and sex (p-value, test for interaction > 0.05) hence analyses were not stratified. Tetrachoric correlations between individual social risk factors were all positive and statistically significant (Table 2).

Table 3 shows the association between the singular social risk factors and death from all-cancers combined, tobacco-related cancers, screening-detectable cancers and site-specific cancers, adjusted for age and sex. Adults with low family income had an increased risk of death from all-cancers combined (HR = 2.1, 95 % CI: 1.6-2.8), tobacco-related cancers (HR = 2.8, 95 % CI: 2.0-4.1), and lung cancer (HR = 2.7, 95 % CI: 1.7-4.3). Adults with low educational level had an increased risk of death from screening-detectable cancers (HR = 2.0 95 % CI: 1.1-3.7), and female breast cancer (HR = 3.0, 95 % CI: 1.3-6.9). Adults belonging to a minority race/ethnic group had an increased risk of death from all-cancers combined (HR = 1.3, 95 % CI: 1.0-1.5), tobacco-related cancers (HR = 1.5, 95 % CI: 1.0-2.1), and screening-detectable cancers (HR = 1.8, 95 % CI = 1.0-1.1). Adults living as single people did not have an increased risk of death from cancer.

Table 4 shows the association between the cumulative social risk and death from all-cancers combined, tobacco-related cancers, screening-detectable cancers and cause-specific cancers. Adults exposed to 3 or more social risk factors were at greater risk of mortality from all-cancers combined (HR = 1.8, 95 % CI: 1.3-2.4), tobacco-related cancers (HR = 2.6, 95 % CI: 1.6-4.0) and lung cancer (HR = 2.3, 95 % CI: 1.3-4.1) compared to adults exposed to no social risk factors. Hazard ratios for deaths from all-cancers combined, tobacco-related cancers, lung cancer significantly increased with an increasing number of social risk factors (all-cancers combined: p for trend = 0.001; tobacco-related cancers: p for trend = <0.001; lung cancer: p for trend = 0.01).

The cumulative effects of social risk factors on death from all-cancers combined, tobacco-related cancers, and lung cancer became non-significant when we controlled for low family income, except for when breast cancer mortality was the outcome (results not shown).

This study finds an increased risk of deaths from all-cancers combined, tobacco-related cancers, and lung cancer with increasing number social risk factors in a large nationally representative sample of U.S. adults. Adults exposed to 3 or more social risk factors had a 1.8-to 2.6-fold increased risk of all-cancer and tobacco-related cancer mortality.

Similar to much of the history of thinking about social disparities in the U.S. [24], research on social disparities and cancer mortality has typically been framed in terms of single social risk factors [25‐28], with a focus on race or education. For example, in a study examining selected cancer mortality rates from 26 U.S. states, educational attainment reported by next of kin was the only indicator of social disadvantage that was used, because this was the only indicator recorded on death certificates [28]. In the U.S. National Longitudinal Mortality Study, the risk of cause-specific cancer mortality was associated with black race [10]. However, as with most such studies, income and education were added as covariates, “isolating” the effect of black race, but providing very little information about the actual risk faced by most black people in the U.S. As we have shown here, social risk factors may co-occur and multiple rather than single social risk factors can have a greater impact on cancer mortality.

We found the cumulative effects of social risk factors on all-cancers combined, tobacco-related cancers, and lung cancer were driven by low family income. Tobacco smoking among low-income adults is known to be more prevalent, but also quit attempts are less likely to be successful [29]. Low-income status can limit monetary resources that can help smokers achieve cessation, limit the person’s capability of utilizing these monetary resources for cessation, as well as influencing the likelihood of predictors of cessation behaviour (e.g. motivational factors, nicotine dependence) [29]. Race/ethnicity and education each contribute to future income level, so this may partly explain why overall and cause-specific cancer mortality was driven to a larger extent by low family income in this middle-to-old aged cohort.

Determining the influence of cumulative social risk on cancer mortality may help inform the design of effective interventions to address social disparities in cancer mortality in the U.S. Recently, the US Preventative Services Task Force (USPSTF) has recommended annual screening for lung cancer with low-dose computed tomography in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years [30]. It has been suggested that it might be also important to monitor lung cancer incidence and stage at diagnosis by race so that resources can be put in place to identify groups that may need targeted screening efforts [31, 32]. However, only monitoring race without taking into account financial barriers may not itself be very effective in eliminating the disparity in lung cancer mortality. The reason is that policies primarily targeted to an individual social risk factor may not fundamentally address issues related to other social risk factors among the proportion of socially disadvantaged adults exposed to multiple social risk factors.

A major strength of the study is that we used a cumulative social risk score based on easily-measured social risk factors to prospectively examine the association between cumulative social risk and cancer mortality in a large nationally representative sample of the U.S. population over a sufficiently long period. Furthermore, percentages of death according to site closely reflect published cancer statsitics [33]. However, several limitations of our study merit consideration. First, the small number of deaths limited our power to detect associations between single social risk factor exposures or cumulative exposure to social risk factors and cancer mortality, especially for site-specific cancers. This may also have limited our ability to detect if risk of cancer mortality and each social risk factor was significantly modified by sex. Second, the finding that adults living as single people were not at increased risk of death from cancer, could be because single-living is a poor proxy for social isolation and reduced social support. This may also lead to attenuate any association between exposure to cumulative social risk and cancer mortality. A meta-analytic review examining the extent to which social relationships influence the risk for mortality, found that the association was strongest for more complex measures of social integration [34]. Third, the use of a cumulative social risk score, such as this, acknowledges that social risk factors tend to co-occur and also makes the implicit assumption that each form of social risk factor carries the same level of risk on cancer mortality. Weighting the cumulative social risk score might be useful in this scenario, however there are several important caveats to doing this. Given that proposed weights are based on the relative association of each social risk factor with the outcome, different weights would end up being proposed for different cancer mortality outcomes for the same social risk factors. Also, specific weights for social risk factors would be given based on specific datasets. Thus, it is not certain that weights derived from this dataset would be generalizable to another dataset. Moreover, considering that these social risk exposures occur across the life course, longitudinal analyses from earlier in the life course would be required in order to more fully understand the contemporaneous and cumulative impact of multiple social risk factor exposure that may underlie social disparities in cancer mortality. We also made the assumption that that components of the cumulative social risk metric have no temporal order. Exposure to one social risk factor may lead to another social risk factor and thus tend to co-occur (chains of risk), or social risk factors may follow one another sequentially but risk of mortality is not increased until the effect of the final exposure in the chain (“trigger effect”) [35]. Chronicity of exposure to social risk factors are also ignored in the cumulative social risk score, and may also be important for influencing cancer mortality. Future research might overcome some of the aforementioned concerns, by collecting data on the age of when the adult was exposed to a specific social risk factor. Fourth, we were not able to examine the potential contribution of mediators including cigarette smoking, obesity, poor diet, physical inactivity, health insurance status and occupational exposures either because of the high percentage of missing data on these variables in the dataset or lack of availability. Finally, those with missing information were more likely to belong to a minority race/ethnic group, have a low education level, be living as a single person and have higher mortality. Thus, the current findings are probably underestimates of the true magnitude of the association between cumulative social risk and cancer mortality. We also acknowledge the possibility that residual confounding may attenuate the strong HRs estimates in this study.

We found that exposure to an increasing number of social risk factors increased the risk of death from all-cancers combined, tobacco-related cancers, and lung cancer in U.S. adults. Future research on the multiple social risk factor exposure earlier in the life course is required in order to better understand the association between cumulative social risk and cancer mortality in the U.S.