Increased Risk Of Cancer Mortality Research Articles

Abstract C107: Racial differences in associations between chemical exposures and cancer-specific mortality

Abstract We lack knowledge of environmental drivers (e.g. chemical exposures) of cancer mortality, which is most often due to the development of metastatic disease. Thus, there is a need to identify associations between chemical exposures and cancer mortality to help prioritize chemicals for further toxicological and epidemiological studies. We aimed to characterize how the associations between chemical biomarker levels and cancer-specific mortality differ by race/ethnicity to identify which concentrations are associated with increased risk for cancer death for each race/ethnicity. We studied 241 toxicant biomarkers in 35,132 participants sampled from the US CDC National Health and Nutrition Examination Survey 1999-2014. We deployed a series of Cox proportional hazard models with mortality status for cancer and time to death as the outcome variables and the chemical concentrations as the main predictor for each race/ethnicity. We adjusted for covariates such as age, sex, poverty income ratio, smoking, and comorbidity. For non-Hispanic Black participants, we found that an increase of one standard deviation in methyl paraben, a compound used in personal care product, is associated with a 60% increase in risk for cancer death (FDR-adjusted p-value = 4.22E-04). In addition, increased levels of lead and cadmium are associated with increased cancer mortality risk. The hazard ratio for an increase in one standard deviation of lead is 1.21 (FDR-adjusted value = 7.16E-06) in non-Hispanic Blacks and is 1.14 (FDR-adjusted p-value = 5.71E-04) in non-Hispanic Whites. The hazard ratio for cadmium is 1.37 (FDR-adjusted value = 3.06E-06) in non-Hispanic Blacks and is 1.26 (FDR-adjusted p-value = 9.23E-07) in non-Hispanic Whites. According to the International Agency for Research on Cancer (IARC) and the US National Toxicology Program (NTP), cadmium is a known carcinogen, and lead is a probable carcinogen. Methyl paraben is not even listed as a probable or known carcinogen but shows higher cancer mortality risk compared to those of lead and cadmium. In addition, the effect of methyl paraben on cancer have not been well studied. Thus, our methodology can help identify chemical contributors to cancer mortality for further mechanistic evaluation. Citation Format: Vy K. Nguyen, Chirag J. Patel, Olivier Jolliet, Justin Colacino. Racial differences in associations between chemical exposures and cancer-specific mortality [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C107.

Prior cancer diagnosis and mortality profile in US adults

BackgroundMortality profiles with multivariate adjustment in patients with a prior cancer diagnosis are scarce. This study aimed to investigate multivariate-adjusted mortality profile in US adults with a prior cancer diagnosis. MethodsThis cohort study included 58,109 US adults (5,016 with a prior cancer diagnosis) who attended the National Health and Nutrition Examination Survey. Mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) of prior cancer diagnosis for mortality. ResultsThis cohort was followed up for 646,033 person-years with a mean follow-up of 11.1 years. Compared with those without cancer, participants with a prior cancer diagnosis had increased crude cumulative mortality rates in each leading cause. Prior cancer diagnosis was associated with a higher multivariate-adjusted risk of mortality from all causes (HR, 1.29; 95% CI, 1.22-1.35), cancer (HR, 2.32; 95% CI, 2.10-2.56), and accidents (HR, 1.90; 95% CI, 1.34-2.68). Prior cancer diagnosis-associated increase in accident mortality appeared only in males and was significant only in non-Hispanic black participants. Prior cancer diagnosis-associated increase in cancer mortality appeared high in non-Hispanic black participants. ConclusionsThis study found that patients with a prior cancer diagnosis had higher multivariate-adjusted accident mortality risks, suggesting that oncologists may need to evaluate accident risks in cancer patients and provide preventive interventions in particular for male and non-Hispanic black patients. Increased cancer mortality risk associated with prior cancer diagnosis in non-Hispanic black participants may also need clinical attention.

The association between biomarkers of acrylamide and cancer mortality in U.S. adult population: Evidence from NHANES 2003-2014.

The association between acrylamide (AA) and the development of cancer has been extensively discussed but the results remained controversial, especially in population studies. Large prospective epidemiological studies on the relationship of AA exposure with cancer mortality were still lacking. Therefore, we aimed to assess the association between AA biomarkers and cancer mortality in adult population from National Health and Nutrition Examination Survey (NHANES) 2003-2014. We followed 3717 participants for an average of 10.3 years. Cox regression models with multivariable adjustments were performed to determine the relationship of acrylamide hemoglobin adduct (HbAA) and glycidamide hemoglobin adduct (HbGA) with cancer mortality. Mediation analysis was conducted to demonstrate the mediated role of low-grade inflammation score (INFLA-score) in this correlation. Compared with the lowest quintile, participants with the highest quintile of HbAA, HbGA and HbAA+HbGA had increased cancer mortality risk, and the hazard ratios(HRs) were 2.07 (95%CI:1.04-4.14) for HbAA, 2.39 (95%CI:1.29-4.43) for HbGA and 2.48 (95%CI:1.28-4.80) for HbAA+HbGA, respectively. And there was a considerable non-linearity association between HbAA and cancer mortality (p for non-linearity = 0.0139). We further found that increased INFLA-score significantly mediated 71.67% in the effect of HbGA exposure on increased cancer mortality risk. This study demonstrates that hemoglobin biomarkers of AA are positively associated with cancer mortality in adult American population and INFLA-score plays a mediated role in this process. Our findings can raise public awareness of environmental and dietary exposure to acrylamide and remind people to refrain from smoking or having acrylamide-rich foods.

Abstract 5894: Synergism between medium-chain fatty acid intake and global magnesium status on the risk of cancer mortality in the National Health and Nutrition Examination Survey (NHANES) 2005-2014

Abstract Medium-chain fatty acids (MCFAs), a class of saturated fatty acids that exist naturally in dairy products and tropical oils, can regulate inflammation, insulin resistance, and immune response. Furthermore, in vitro and in vivo studies found MCFAs have strong anticarcinogenic properties. Recent evidence reveals MCFAs inhibits aerobic glycolysis in tumor cells. It is conceivable that MCFAs have an “anti-Warburg effect”. In a double-blind randomized trial (Personalized Prevention of Colorectal Cancer; NCT01105169), we found that 12-week personalized magnesium (Mg) supplementation led to significantly increased circulating levels of MCFAs, particularly caprylic acid (C8:0), which was due to enhanced microbial production. These novel findings suggest individuals with Mg sufficiency can receive supplies of MCFAs from microbiome whereas people with Mg deficiency cannot and so need MCFAs from intake. Thus, we hypothesized that the associations between intakes of C8:0 and risk of cancer mortality are modified by body Mg status. We tested this hypothesis in the NHANES, a nationally representative study. We recently developed the Mg depletion score (MDS) to assess Mg status and validated it against the invasive gold standard measure of Mg status. MDS performs better than either serum Mg or Mg intake at predicting Mg deficiency. We also found higher Mg intake was associated with reduced risks of inflammation and total mortality only among those with higher MDS scores, i.e., higher risk of losing Mg in the kidney. Thus, we examined if MDS modified the associations between intakes of MCFAs and risk of cancer mortality. Among 11,890 US adults aged ≥20 years over a median follow-up of 70 person-months, the associations between C8:0 intake and cancer mortality risk differed by MDS (Pinteraction=0.12). Higher C8:0 intake was associated with increased cancer mortality risk when MDS=0 (no risk of losing Mg; P-trend=0.03) after adjusting for all covariates, including dairy product intake. C8:0 intake was not related to risk of cancer mortality when MDS=1. Conversely, C8:0 intake may be associated with a reduced cancer mortality risk among those with MDS>1(high risk of losing Mg). In particular, higher C8:0 intake was significantly associated with a reduced risk of cancer mortality (P-trend<0.01) with an HR (95% CI) of 0.11 (0.02-0.84) for the highest quartile of C8:0 intake when Mg intake was above the Estimated Average Requirement. No associations were found for intakes of C6:0, C10:0 and C12:0. In summary, C8:0 can be generated by human gut microbiome through optimized Mg consumption; dietary intakes of C8:0 were associated with a reduced risk of cancer mortality among those at high risk of losing Mg, but with adequate Mg consumption; and intakes of C8:0 were related to an increased risk of cancer mortality among those with no risk of losing Mg. Citation Format: Lei Fan, Xiangzhu Zhu, Alexandra Shingina, Lihua Shu, Martha Shrubsole, Qi Dai. Synergism between medium-chain fatty acid intake and global magnesium status on the risk of cancer mortality in the National Health and Nutrition Examination Survey (NHANES) 2005-2014 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5894.

Association of Blood Trihalomethane Concentrations with Risk of All-Cause and Cause-Specific Mortality in U.S. Adults: A Prospective Cohort Study.

Water chlorination can lead to the formation of disinfection byproducts, including trihalomethanes (THMs). However, few epidemiologic studies have explored associations between THM exposure and mortality. This study included 6720 adults aged ≥40 years from the National Health and Nutrition Examination Survey 1999-2012 who had blood THM concentrations quantified. A higher risk of all-cause mortality was found across increasing quartile concentrations of blood chloroform (TCM) and total THMs (TTHMs; sum of all four THMs) (both p for trend = 0.02). Adults in the highest quartile of TCM and TTHM concentrations had hazard ratios (HRs) of 1.35 (95% confidence intervals: 1.05-1.74) and 1.37 (1.05-1.79), respectively, for all-cause mortality, compared with adults in the lowest quartile. When cause-specific mortality was evaluated, a positive relationship was found between blood bromodichloromethane (BDCM), dibromochloromethane (DBCM), bromoform (TBM), total brominated THMs (Br-THMs; sum of BDCM, DBCM, and TBM), and TTHM concentrations and risk of cancer death and between blood TCM and TTHMs and risk of other cause (noncancer/nonheart disease) mortality. Our findings suggest that higher exposure to Br-THMs was associated with increased cancer mortality risk, whereas TCM was associated with a greater risk of noncancer/nonheart disease mortality.

Association between proximity to industrial chemical installations and cancer mortality in Spain

It is likely that pollution from chemical facilities will affect the health of any exposed population; however, the majority of scientific evidence available has focused on occupational exposure rather than environmental. Consequently, this study assessed whether there could have been an excess of cancer-related mortality associated with environmental exposure to pollution from chemical installations – for populations residing in municipalities in the vicinity of chemical industries. To this end, we designed an ecological study which assessed municipal mortality due to 32 types of cancer in the period from 1999 to 2008. The exposure to pollution was estimated using distance from the facilities to the centroid of the municipality as a proxy for exposure. In order to assess any increased cancer mortality risk in municipalities potentially exposed to chemical facilities pollution (situated at a distance of ≤5 km from a chemical installation), we employed Bayesian Hierarchical Poisson Regression Models. This included two Bayesian inference methods: Integrated Nested Laplace Approximations (INLA) and Markov Chain Monte Carlo (MCMC, for validation). The reference category consisted of municipalities beyond the 5 km limit. We found higher mortality risk (relative risk, RR; estimated by INLA, 95% credible interval, 95%CrI) for both sexes for colorectal (RR, 1.09; 95%CrI, 1.05–1.15), gallbladder (1.14; 1.03–1.27), and ovarian cancers (1.10; 1.02–1.20) associated with organic chemical installations. Notably, pleural cancer (2.27; 1.49–3.41) in both sexes was related to fertilizer facilities. Associations were found for women, specifically for ovarian (1.11; 1.01–1.22) and breast cancers (1.06; 1.00–1.13) in the proximity of explosives/pyrotechnics installations; increased breast cancer mortality risk (1.10; 1.03–1.18) was associated with proximity to inorganic chemical installations. The results suggest that environmental exposure to pollutants from some types of chemical facilities may be associated with increased mortality from several different types of cancer.

The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis.

BackgroundTelomeres are essential for chromosomal integrity and stability. Shortened telomere length (TL) has been associated with risk of cancers and aging-related diseases. Several studies have explored associations between TL and cancer prognosis, but the results are conflicting.MethodsProspective studies on the relationship between TL and cancer survival were identified by a search of PubMed up to May 25, 2015. There were no restrictions on the cancer type or DNA source. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis approaches were conducted to determine pooled relative risks and 95% confidence intervals.ResultsThirty-three articles containing forty-five independent studies were ultimately involved in our meta-analysis, of which twenty-seven were about overall cancer survival and eighteen were about cancer progression. Short TL was associated with increased cancer mortality risk (RR = 1.30, 95%CI: 1.06–1.59) and poor cancer progression (RR = 1.44, 95%CI: 1.10–1.88), both with high levels of heterogeneity (I2 = 83.5%, P = 0.012for overall survival and I2 = 75.4%, P = 0.008 for progression). TL was an independent predictor of overall cancer survival and progression in chronic lymphocytic leukemia. Besides, short telomeres were also associated with increased colorectal cancer mortality and decreased overall survival of esophageal cancer, but not in other cancers. Cancer progression was associated with TL in Asian and America populations and short TL predicted poor cancer survival in older populations. Compared with tumor tissue cells, TL in blood lymphocyte cells was better for prediction. In addition, the associations remained significant when restricted to studies with adjustments for age, with larger sample sizes, measuring TL using southern blotting or estimating risk effects by hazard ratios.ConclusionShort TL demonstrated a significant association with poor cancer survival, suggesting the potential prognostic significance of TL. Additional large well-designed studies are needed to confirm our findings.

Cumulative radiation dose from medical imaging in kidney transplant patients

Although many patients undergoing kidney transplant are exposed to multiple examinations that increase cumulative effective doses (CEDs) of ionizing radiation, no data are available characterizing their total longitudinal radiation burden and relating radiation burden with risk factors for more exposure. We did a retrospective cohort study of 92 patients (mean age 52 years; range: 20-75 years) who underwent kidney transplant at University Hospital, Novara, Italy, that evaluated all following medical imaging procedures involving ionizing radiation undergone beginning June 2007, and all subsequent procedures through August 2011, at the centre. The mean and median annual CED were 17.2 and 4.9 millisieverts (mSv) per patient-year. The mean and median total CED per patient over the study period were 46.1 and 17.3 mSv, respectively. Twenty-eight and 12% of patients had total CED >50 and 100 mSv, values which are associated with a good or strong evidence of an increased cancer mortality risk, respectively. Computed tomography scanning accounted for 73% of the total CED. The annual CED was significantly higher in incident patients and in patients with ischaemic heart disease and cancer. In this institution, multiple testing of kidney transplant patients was common in many patients associated with high cumulative estimated doses of ionizing radiation.

Cancer mortality after nasopharyngeal radium irradiation in the Netherlands: a cohort study.

Nasopharyngeal radium irradiation (NRI) was used widely from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for cancer-related deaths than were nonexposed individuals. We conducted a retrospective cohort study of all-cause and cancer-related mortality in 5358 NRI-exposed subjects and in 5265 frequency-matched nonexposed subjects, who as children were treated at nine ear, nose, and throat clinics in The Netherlands from 1945 through 1981. We recorded personal and medical data from original patient medical records and assessed vital status through follow-up at municipal population registries. Risk of mortality was evaluated by standardized mortality ratios (SMRs). All statistical tests were two-sided. The average radiation doses were 275, 10.9, 1.8, and 1.5 cGy for the nasopharynx, pituitary, brain, and thyroid, respectively. The median follow-up was 31.6 years. Three hundred two NRI-exposed subjects had died, with 269.2 deaths expected (SMR = 1.1; 95% confidence interval [CI] = 1.0 to 1.3); among nonexposed subjects, 315 died, with 283.5 deaths expected (SMR = 1.1; 95% CI = 0.99 to 1.2). Cancer-related deaths of 96 exposed subjects (SMR = 1.2; 95% CI = 0.95 to 1.4) and 87 nonexposed subjects (SMR = 1.0; 95% CI = 0.8 to 1.3) were documented. There were no excess deaths from cancers of the head and neck area among exposed subjects. However, there were excess deaths from cancers of lymphoproliferative and hematopoietic origin (SMR = 1.9; 95% CI = 1.1 to 3.0), mainly from non-Hodgkin's lymphoma (SMR = 2.6; 95% CI = 1.0 to 5.3). We found no evidence that breast cancer deaths were less than expected (SMR = 1.7; 95% CI = 0.9 to 2.8) in contrast to an earlier study. Our findings do not indicate an increased cancer mortality risk in a population exposed to NRI in childhood. More prolonged follow-up of this and other NRI cohorts is recommended.

Body mass index at the age of 18 and its effects on 32-year-mortality from coronary heart disease and cancer A nested case-control study among the entire 1932 Dutch male birth cohort

In a nested case-control design the Body Mass Index at 18 years of age was related to 32-year mortality from coronary heart disease (ICD-codes: 410–414) and cancer (ICD-codes: 140–208) among the 1932 Dutch male birth cohort. By means of a logistic regression model the risk ratios were estimated for four BMI-categories: ⩽ 18.99, 19.00–19.99, 20.00–24.99, ⩾25.00. Information on blood pressure, resting heart rate, initial health status, education and region of origin was available and these factors were taken into account as possible confounders. The mortality rate for coronary heart disease was highest for the men in the fattest group, while the leanest group showed an excess cancer mortality. The adjusted coronary heart disease mortality risk ratio was elevated for both BMI-categories above the reference category of 19.00–19.99, with an estimate of 2.5 for the men with a BMI ⩾ 25.00 at the age of 18. An increased cancer mortality risk ratio of 1.4, mainly due to lung cancer, was observed during the last 20 years of the 32-year follow-up period for the men with a BMI ⩽18.99. The importance of age and differentiation of causes of death in interpreting the results of prospective studies is discussed.

Growth of Polish children aged 0–2 years at the beginning of the economic crisis

In a nested case-control design the Body Mass Index at 18 years of age was related to 32-year mortality from coronary heart disease (ICD-codes: 410–414) and cancer (ICD-codes: 140–208) among the 1932 Dutch male birth cohort. By means of a logistic regression model the risk ratios were estimated for four BMI-categories: ⩽ 18.99, 19.00–19.99, 20.00–24.99, ⩾25.00. Information on blood pressure, resting heart rate, initial health status, education and region of origin was available and these factors were taken into account as possible confounders. The mortality rate for coronary heart disease was highest for the men in the fattest group, while the leanest group showed an excess cancer mortality. The adjusted coronary heart disease mortality risk ratio was elevated for both BMI-categories above the reference category of 19.00–19.99, with an estimate of 2.5 for the men with a BMI ⩾ 25.00 at the age of 18. An increased cancer mortality risk ratio of 1.4, mainly due to lung cancer, was observed during the last 20 years of the 32-year follow-up period for the men with a BMI ⩽18.99. The importance of age and differentiation of causes of death in interpreting the results of prospective studies is discussed.