The relationship between psychological stress and cancer incidence: a systematic review and meta-analysis

BackgroundThe Ministry of Civil Affairs of the People’s Republic of China reported that in 2018, 6.97 million left-behind children (LBC), children who live in rural areas away from their parents, were being cared for by grandparents, relatives, elder siblings, or often living alone. Their parents have migrated to cities for better income opportunities. While a number of studies have detailed elevated depressive symptoms among LBC, relatively little is known about the causes of poorer mental health in LBC.MethodsThis study used longitudinal data to examine associations between peer victimization, stressful life events, and depressive symptom severity in LBC from four randomly-selected middle schools in Guizhou Province, China. A total of 862 children aged 11–18 years, with 472 LBC (54.76%) and 390 non-left-behind children (NLBC) (45.24%), were included in the analysis. T-test was used to compare the depressive symptoms, peer victimization, and stressful life events between LBC and NLBC at baseline and follow-up (6 months later). Multivariable linear regression models were used to examine the mediation effect of follow-up stressful life events on the relationship between baseline peer victimization and follow-up depressive symptoms among LBC.ResultsResults suggested that LBC had higher peer victimization and stressful life events than NLBC (β = 1.28, p = 0.04), and peer victimization and stressful life events at baseline were associated with increased follow-up depressive symptoms among LBC (Peer victimization: β = 0.25, p < 0.0001; Stressful life events: β = 0.15, p < 0.001). Peer victimization affected depressive symptoms partially through stressful life events for female LBC and completely through stressful life events for male LBC, controlling for age, perceived socioeconomic status, and school.ConclusionsThis study highlights the vulnerability of LBC exhibiting negative mental health outcomes as they were found to experience more peer victimization and feel more stressed when stressful life events happened, compared with NLBC. Results of this study suggested that protecting LBC from peer victimization experiences can potentially prevent LBC from experiencing an increased impact of other stressful life events, thus decreasing the likelihood of their depressive symptoms. Intervention design should consider the different mediating effects of stressful life events on the relationship between peer victimization and depressive symptoms among female and male LBC.

This study aimed to investigate the association between lifetime cumulative and domain-specific stressful life events (SLEs) and suicidality in individuals with first-episode psychosis (FEP), while accounting for sociodemographic, clinical and psychosocial characteristics. A descriptive, cross-sectional study was conducted with 97 individuals with FEP (34 females, 63 males) aged 13-51 years from the PROFEP study in Barcelona, Spain. SLEs were assessed with the Questionnaire of Stressful Life Events (QSLE) and suicidality with the Plutchik Scale of Suicide Risk (RS). Multivariate regression models examined associations between SLEs and suicidality, adjusting for sociodemographic, clinical and psychosocial characteristics. Higher cumulative SLEs were associated with increased suicide risk and with suicide attempts (p = 0.020; p = 0.029, OR = 1.125). Partner- and legal-related SLEs were linked to greater suicide risk (p = 0.022; p = 0.035), whereas educational and family SLEs were linked to suicide attempts (p = 0.034, OR = 2.350; p = 0.004, OR = 2.065). SLEs were not associated with suicidal ideation. Suicide risk was associated with depression and increased perceived stress (both p = < 0.001), suicidal ideation with higher perceived stress and younger age (p = 0.005, OR = 1.107; p = 0.043, OR = 0.935) and suicide attempts with depression and male sex (p = 0.002, OR = 12.493; p = 0.029, OR = 0.075). Cumulative and domain-specific SLEs, particularly interpersonal, educational and legal events, play a significant role in suicide risk and suicide attempts in FEP. Perceived stress, depression and sociodemographic factors are also associated with suicidality in this population. These findings highlight the importance of screening for SLEs and suicidality and implementing stress-management interventions.

Stressful life events are associated with the onset of episodes of major depression. However, exposure to stressful life events is influenced by genetic factors, and these factors are correlated with those that predispose to major depression. The aim of this study was to clarify the degree to which stressful life events cause major depression. The authors assessed the occurrence of 15 classes of stressful life events and the onset of DSM-III-R major depression over a 1-year period in female twins ascertained from a population-based registry. The sample contained 24,648 person-months and 316 onsets of major depression. Stressful life events were individually rated on contextual threat and dependence (the degree to which the stressful life event could have resulted from the respondent's behavior). The nature of the relationship between stressful life events and major depression was tested by 1) discrete-time survival analysis examining the relationship between dependence and the depressogenic effect of stressful life events and 2) a co-twin control analysis. While independent stressful life events were significantly associated with onsets of depression, when level of threat was controlled, the association was significantly stronger for dependent events. The odds ratio for onset of major depression in the month of a stressful life event was 5.64 in all subjects, 4.52 within dizygotic pairs, and 3.58 within monozygotic pairs. Stressful life events have a substantial causal relationship with the onset of episodes of major depression. However, about one-third of the association between stressful life events and onsets of depression is noncausal, since individuals predisposed to major depression select themselves into high-risk environments.

Introduction: Carriers of germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) have a high risk of colorectal and other cancers (Lynch syndrome). Between 30% and 70% of carriers will be develop colorectal cancer by age 70 if they are not screened for the disease. What is not well understood is how the effect of mutations, in absolute and relative terms, varies by age. Methods: We conducted a literature review to identify studies of colorectal cancer that estimated age-specific hazard ratios for colorectal cancer for carriers of a mutation in MLH1 or MSH2 compared with the general population. Studies were excluded if they did not adjust correctly for ascertainment. We conducted a random effects meta-analysis to estimate the average age-specific hazard ratio. Annual risk (incidence) by multiplying the population incidence by the age-specific hazard ratio estimated by the meta-analysis. Results: We identified six studies comprising 673 families (282 MLH1, 391 MSH2). All studies observed that the hazard ratio for colorectal cancer was highest at young ages and decreased with age. This pattern was observed for both males and females and for both MLH1 and MSH2 mutation carriers. Overall, the hazard ratio dropped 6-8 fold over three decades (Table). Incidence of colorectal cancer for carriers increased until age 40 years for males and 50 years for females, and then plateaued (Table). Conclusion: At younger ages, in multiplicative terms, the magnitude of the increased risk conferred by the mutations is substantially greater than at older ages. The reason for this age-dependency is not known. It is, however, consistent with a multi-stage model of carcinogenesis for Lynch syndrome. These findings add to the complement of factors that complicate risk estimation for Lynch syndrome including: polygenic effects, non-genetic risk modifiers, and the possibility of a parent-of-origin effect. There is still much to learn about the clinical implications and carcinogenesis of Lynch syndrome. Meta-analysis estimates of hazard ratios and incidences for colorectal cancer by age group. 30-39 year olds 40-49 year olds 50-59 year olds 60-69 year olds Hazard ratio (95%CI): Risk of colorectal cancer in carriers/risk for the general population. Males 120 (60-243) 95 (39-226) 33 (14-78) 14 (4.2-51) Females 80 (42-154) 70 (35-139) 28 (19-41) 14 (7.4-26) Incidence: Proportion of carriers diagnosed with colorectal cancer per year. Males 1 in 146 1 in 50 1 in 39 1 in 38 Females 1 in 490 1 in 135 1 in 69 1 in 61 Citation Format: Mark A. Jenkins, Aung Ko Win, James G. Dowty, John D. Mathews, John L. Hopper. Hazard ratio for colorectal cancer risk in Lynch syndrome is inversely associated with age. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4842. doi:10.1158/1538-7445.AM2013-4842

Can selenium supplementation prevent colorectal cancer?

Association between stress, depression or anxiety and cancer: Rapid review of reviews

Background: Healthcare spending for coronary artery disease (CAD)-related services is higher than for other chronic conditions. Diagnosis of incident cancer may impede management of CAD, thereby increasing the risk of CAD-related complications and associated healthcare expenditures. This study examined the relationship between incident cancer and CAD-related expenditures among elderly Medicare beneficiaries. Patients and Methods: A retrospective longitudinal study was conducted using the SEER-Medicare linked registries and a 5% noncancer random sample of Medicare beneficiaries. Elderly fee-for-service Medicare beneficiaries with preexisting CAD and with incident breast, colorectal, or prostate cancer (N=12,095) or no cancer (N=34,237) were included. CAD-related healthcare expenditures comprised Medicare payments for inpatient, home healthcare, and outpatient services. Expenditures were measured every 120 days during the 1-year preindex and 1-year postindex periods. Adjusted relationship between incident cancer and expenditures was analyzed using the generalized linear mixed models. Results: Overall, CAD-related mean healthcare expenditures in the preindex period accounted for approximately 32.6% to 39.5% of total expenditures among women and 41.5% to 46.8% among men. All incident cancer groups had significantly higher CAD-related expenditures compared with noncancer groups (P<.0001). Men and women with colorectal cancer (CRC) had 166% and 153% higher expenditures, respectively, compared with their noncancer counterparts. Furthermore, men and women with CRC had 57% and 55% higher expenditures compared with those with prostate or breast cancer, respectively. Conclusions: CAD-related expenditures were higher for elderly Medicare beneficiaries with incident cancer, specifically for those with CRC. This warrants the need for effective programs and policies to reduce CAD-related expenditures. Close monitoring of patients with a cancer diagnosis and preexisting CAD may prevent CAD-related events and expenditures.

This study used the social support effectiveness framework to examine whether effective social support buffered the relationship between stressful life events and distress among hematopoietic stem cell transplant (HSCT) survivors and whether that buffering effect depended on the type of caregiver who provided it (partner versus non-partner caregivers). A total of 275 HSCT survivors completed measures of the effectiveness of their caregiver's support-social support effectiveness (SSE)-distress, and stressful life events. Hierarchical linear regression was used to analyze a three-way interaction between stressful life events, caregiver SSE, and caregiver type on distress. After controlling for covariates, the three-way interaction of stressful life events, caregiver SSE, and caregiver type was significant (b = - 0.21, SE = 0.00, p < 0.001). Among partnered survivors, more stressful life events were associated with greater distress (B = 0.03, SE = 0.01, p = 0.045) when caregiver SSE was low. There was no association between stressful life events and distress when caregiver SSE was average (B = 0.01, SE = 0.01, p = 0.50) or high (B = - 0.01, SE = 0.02, p = 0.61). Among non-partnered survivors, there was a positive association between stressful life events and distress regardless of caregiver SSE. Average or highly effective caregiver support buffered effects of stressful life events on distress among partnered survivors. There was no evidence that support at any level of effectiveness buffered stressful life events among non-partnered survivors. Findings highlight the importance of measuring social support effectiveness and source of support among HSCT survivors.

The Center for Global Early Detection at MD Anderson has initiated two longitudinal early detection studies: LEAP (Lung Cancer Early Detection and Prevention, 2013-2019) for lung cancer screening and MERIT (Mammography Early Detection Risk Assessment and Imaging Technologies, 2017-ongoing) for breast cancer screening. Both cohorts enrolled subjects based on US standard-of-care guidelines at the time of enrollment for low-dose CT screening and mammography, respectively. The cohorts collected detailed health data from questionnaires, imaging data, and blood specimens at the time of screening. In addition to information on the screened-detected cancers, follow-up information was collected on any other types of cancers that are diagnosed after enrollment. Here, we evaluate the incidence of other cancers without available screening to assess the potential impact of multi-cancer early detection studies for these two types of screening populations. The two studies enrolled approximately 9,300 subjects (N = 2853 for LEAP; N = 6,400 for MERIT) with median follow up times of 2.99 years (IQR: 1.09-4.08) for LEAP and 2.05 years (IQR: 0.09-3.01) for MERIT. Currently, there are more than 800,000 aliquots of banked biospecimens from both cohorts. The incidence of lung cancer for the LEAP cohort undergoing low-dose CT screening was 0.91% per year. Cancers other than lung cancer were also diagnosed after enrollment including prostate, breast, bladder, head, and neck, colorectal, lymphoma, endocrine, gynecologic, and kidney cancers. Overall, the incidence of other cancers in LEAP was high for those cancers without available screening - 0.49% per year excluding breast, prostate, and colorectal cancers. The incidence of breast cancer for women in LEAP was lower than expected, 0.17% per year, likely a result of underscreening by mammography. For the MERIT cohort, the incidence of breast cancer was 0.89% per year. Cancers other than breast were diagnosed in MERIT after enrollment including gynecologic, melanoma, lung, colorectal, endocrine, bladder, and gastrointestinal cancers. The incidence of other cancers in MERIT was 0.55% per year, excluding colorectal cancer. We conclude that the incidence of cancers without a current screening modality in LEAP and MERIT is sufficiently high (0.49-0.55% per year) to justify the application of multi-cancer screening. Even for cancers with standard-of-care screening, a multi-cancer blood-based biomarker test could be useful given the possibility of underscreening, as we observed for breast cancer in the LEAP cohort. Citation Format: Jennifer Dennison, Ehsan Irajizad, Edwin Ostrin, Myrna Godoy, Olena Weaver, Jessica Leung, Samir Hanash. Application of multi-cancer early detection to lung and breast cancer screening populations. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P057.

Gamma-glutamyl transferase (GGT) has been shown to have associations with several diseases including cancers. Previous studies have investigated the effect of GGT levels on the gastrointestinal (GI) cancer incidence. We aim to systematically investigate these studies to provide better insights into the interrelationship between GGT and GI cancers. Online databases were searched to find relevant studies investigating different GGT levels' effects on the incidence of GI cancers including colorectal, esophageal, liver, pancreas, gastric, and biliary duct cancers. Random-effect meta-analysis was conducted to pool the hazard ratios (HRs) of GGT quartiles (Qs) effect on cancer incidence. A total of 26 studies were included in the final review, 12 of which underwent meta-analysis that investigated 11 million patients. Based on the meta-analysis, Q4 patients had a 69% higher hazard of GI cancer incidence (HR 1.69, 95% CI 1.41-2.02, p-value < 0.001). The hazard ratio significance was also similar for Q3 (HR 1.22, 95% CI 1.15-1.30, p-value < 0.001) and Q2 (HR 1.10, 95% CI 1.05-1.16, p-value =0.002) of GGT. Colorectal and liver cancers showed a higher hazard ratio among Q2, Q3, and Q4 of GGT compared to Q1. In pancreas and bile duct cancers, only Q4 of GGT had significantly higher HR. Q3 and Q4 of GGT levels had statistically significant associations with gastric cancer incidence. Higher GGT levels correlate with higher rates of GI cancer incidence, especially in colorectal and hepatic cancers. Future studies should investigate this biomarker's potential role in risk assessment for digestive cancers.

Stressful life events, long-term difficulties, and high neuroticism are established risk factors for depression. Less is known about their role in late-life depression, how they modify or mediate one another's effects, and whether this differs between major and subsyndromal, first and recurrent episodes. The authors used a prospective case-control design nested in a community survey of elderly subjects that included a measure of neuroticism. They compared 83 survey participants who subsequently developed a depressive episode with 83 randomly selected comparison participants. The authors determined dates of onset, history, and severity of episodes and dates of occurrence and severity of stressful life events and difficulties. Stressful life events did not mediate the effects of high neuroticism and difficulties at onset, possibly because of the uncontrollable nature of common stressful life events in later life. Without both high neuroticism and difficulties, stressful life events did not increase risk. High neuroticism and difficulties increased risk, even without a stressful life event. In the presence of high neuroticism and/or difficulties, the depressogenic effect of stressful life events was substantial, suggesting effect modification. The authors found no evidence to suggest etiological discontinuity between major and subsyndromal episodes. First and recurrent episodes showed a discontinuous pattern of associations. Severe stressful life events had weaker associations, but high neuroticism and mild stressful life events had stronger associations with recurrent than with first episodes. This study demonstrated the usefulness of a dynamic stress-vulnerability model for understanding late-life depression. Evidence was found suggesting etiological discontinuity between first and recurrent but not between major and subsyndromal episodes.

Guidelines on genetic evaluation and management of Lynch syndrome: A consensus statement by the U.S. Multi-Society Task Force on Colorectal Cancer

Background: Colorectal cancer (CRC) is the 3rd most diagnosed cancer worldwide. When considered separately, both neighborhood- and individual-level SES exposures have been associated with CRC incidence. However, the joint associations of neighborhood- and individual-level SES on CRC incidence have not been examined. Methods: In a prospective study of 153,725 Multiethnic Cohort (MEC) participants (24,764 African American, 44,447 Japanese American, 34,974 Latino, 11,511 Native Hawaiian, and 38,029 White participants) recruited from predominantly Los Angeles County, California (CA), and Hawaii (HI), we examined the joint association of neighborhood SES (nSES) and individual-level education with CRC incidence (CA: 2,519, HI: 2,210 cases). Education, other demographics, and health behaviors were self-reported in the baseline questionnaire (1993-1996). CRC diagnosis was determined via linkages with state cancer registries. nSES was derived using a composite score based on 1990 US Census block group data and assigned to geocoded baseline addresses. Our joint SES measure included four categories: high nSES (quintiles 4-5) and high education (&amp;gt; high school), high nSES and low education (≤ high school), low nSES (quintiles 1-3) and high education, and low nSES and low education. State-specific hazards ratios (HR) for CRC incidence were estimated for joint SES categories. Cox regression adjusted for age at cohort entry, CRC family history, polyp history, obesity, diabetes, diet, alcohol, smoking, physical activity, and NSAID, multivitamin, and hormone therapy use. Subgroup analyses were conducted by sex, race, and ethnicity. Results: For HI MEC participants, compared to individuals with high nSES and high education, risk for CRC was highest among those with low nSES and low education (HR=1.27; 95% CI:1.11-1.45) followed by high nSES and low education (HR=1.25; 95% CI:1.12-1.41), and low nSES and high education (HR=1.17; 95% CI: 1.03-1.31). This pattern of association was observed across sex but differed across race and ethnicity (p-heterogeneity=0.04). The overall pattern of association was observed among White participants in HI. However, for Japanese American individuals in HI, compared to those with high nSES and high education, risk for CRC was highest for low nSES and high education (HR=1.29; 95% CI:1.09-1.53) and high nSES and low education (HR= 1.28; 95% CI; 1.10-1.50). For Native Hawaiian individuals, compared to those with high nSES and high education, CRC risk was highest for those with low nSES and low education (HR=1.70; 95% CI: 1.20-2.42). Associations were not statistically significant between the joint SES measure and CRC risk in CA (HRs: 0.92-0.97). Conclusion: Among MEC participants in HI, CRC risk varied with the joint measure of nSES and education across racial and ethnic groups. These findings emphasize the importance of considering the joint associations of neighborhood- and individual-level SES in understanding racial and ethnic disparities in CRC. Citation Format: Catherine Walsh, Meera Sangaramoorthy, Songyi Park, Sung-shim (Lani) Park, Gertraud Maskarinec, Lynne Wilkens, Christopher Haiman, Anna Wu, Salma Shariff-Marco, Loic Le Marchand, Iona Cheng. Joint Associations of Neighborhood Socioeconomic Status and Education on the Incidence of Colorectal Cancer: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B152.

Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After Surgery' programmes, which include multimodal interventions, have improved patient outcomes substantially. However, these are mainly applied peri- and postoperatively. Multimodal prehabilitation includes multiple preoperative interventions to prepare patients for surgery with the aim of increasing resilience, thereby improving postoperative outcomes. To determine the effects of multimodal prehabilitation programmes on functional capacity, postoperative complications, and quality of life in adult patients undergoing surgery for colorectal cancer. We searched CENTRAL, MEDLINE, Embase and PsycINFO in January 2021. We also searched trial registries up to March 2021. We included randomised controlled trials (RCTs) in adult patients with non-metastatic colorectal cancer, scheduled for surgery, comparing multimodal prehabilitation programmes (defined as comprising at least two preoperative interventions) with no prehabilitation. We focused on the following outcomes: functional capacity (i.e. 6-minute walk test, VO2peak, handgrip strength), postoperative outcomes (i.e. complications, mortality, length of hospital stay, emergency department visits, re-admissions), health-related quality of life, compliance, safety of prehabilitation, and return to normal activities. Two authors independently selected studies, extracted data, assessed risk of bias and used GRADE to assess the certainty of the evidence. Any disagreements were solved with discussion and consensus. We pooled data to perform meta-analyses, where possible. We included three RCTs that enrolled 250 participants with non-metastatic colorectal cancer, scheduled for elective (mainly laparoscopic) surgery. Included trials were conducted in tertiary care centres and recruited patients during periods ranging from 17 months to 45 months. A total of 130 participants enrolled in a preoperative four-week trimodal prehabilitation programme consisting of exercise, nutritional intervention, and anxiety reduction techniques. Outcomes of these participants were compared to those of 120 participants who started an identical but postoperative programme. Postoperatively, prehabilitation may improve functional capacity, determined with the 6-minute walk test at four and eight weeks (mean difference (MD) 26.02, 95% confidence interval (CI) -13.81 to 65.85; 2 studies; n = 131; and MD 26.58, 95% CI -8.88 to 62.04; 2 studies; n = 140); however, the certainty of evidence is low and very low, respectively, due to serious risk of bias, imprecision, and inconsistency. After prehabilitation, the functional capacity before surgery improved, with a clinically relevant mean difference of 24.91 metres (95% CI 11.24 to 38.57; 3 studies; n = 225). The certainty of evidence was moderate due to downgrading for serious risk of bias. Prehabilitation may also result in fewer complications (RR 0.95, 95% CI 0.70 to 1.29; 3 studies; n = 250) and fewer emergency department visits (RR 0.72, 95% CI 0.39 to 1.32; 3 studies; n = 250). The certainty of evidence was low due to downgrading for serious risk of bias and imprecision. On the other hand, prehabilitation may also result in a higher re-admission rate (RR 1.20, 95% CI 0.54 to 2.65; 3 studies; n = 250). The certainty of evidence was again low due to downgrading for risk of bias and imprecision. The effect on VO2peak, handgrip strength, length of hospital stay, mortality rate, health-related quality of life, return to normal activities, safety of the programme, and compliance rate could not be analysed quantitatively due to missing or insufficient data. The included studies did not report a difference between groups for health-related quality of life and length of hospital stay. Data on remaining outcomes were not reported or were reported inadequately in the included studies. Prehabilitation may result in an improved functional capacity, determined with the 6-minute walk test both preoperatively and postoperatively. Complication rates and the number of emergency department visits postoperatively may also diminish due to a prehabilitation programme, while the number of re-admissions may be higher in the prehabilitation group. The certainty of evidence ranges from moderate to very low, due to downgrading for serious risk of bias, imprecision and inconsistency. In addition, only three heterogeneous studies were included in this review. Therefore, the findings of this review should be interpreted with caution. Numerous relevant RCTs are ongoing and will be included in a future update of this review.

Ulcerative colitis with low-grade dysplasia