Relationship Between the Use of Statins and Patient Survival in Colorectal Cancer: A Systematic Review and Meta-Analysis

Background

Studies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear.

Methods

We searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel–Haenszel random-effect modeling. All statistical tests were two-sided.

Results

Four studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use.

Conclusions

Statin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors.     

Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases

This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.     

The effect of diagnostic misclassification on non-cancer and cancer mortality dose response in A-bomb survivors.

We used the EM algorithm in the context of a joint Poisson regression analysis of cancer and non-cancer mortality in the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) to assess whether the observed increased risk of non-cancer death due to radiation exposure (Shimizu et al., RERF Technical Report 02-91, 1991) can be attributed solely to misclassification of cancer as non-cancer on death certificates. We show that greater levels of dose-independent misclassification than are indicated by a series of autopsies conducted on a subset of LSS members would be required to explain the non-cancer dose response, but that a relatively small amount of dose-dependence in the misclassification of cancer would explain the result. The adjustment for misclassification also results in higher risk estimates for cancer mortality. We review applications of similar statistical methods in other contexts and discuss extensions of the methods to more than two causes of death.     

Impact of Uncertainties in Exposure Assessment on Thyroid Cancer Risk among Persons in Belarus Exposed as Children or Adolescents Due to the Chernobyl Accident

BackgroundThe excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of ¹³¹I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error.MethodsWe examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996–2004, who had direct thyroid ¹³¹I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied.ResultsThere was a statistically significant (p<0.001) increasing dose-response for prevalent thyroid cancer, irrespective of regression-adjustment method used. Without adjustment for dose errors the excess odds ratio was 1.51 Gy⁻ (95% CI 0.53, 3.86), which was reduced by 13% when regression-calibration adjustment was used, 1.31 Gy⁻ (95% CI 0.47, 3.31). A Monte Carlo maximum likelihood method yielded an excess odds ratio of 1.48 Gy⁻ (95% CI 0.53, 3.87), about 2% lower than the unadjusted analysis. The Bayesian method yielded a maximum posterior excess odds ratio of 1.16 Gy⁻ (95% BCI 0.20, 4.32), 23% lower than the unadjusted analysis. There were borderline significant (p = 0.053–0.078) indications of downward curvature in the dose response, depending on the adjustment methods used. There were also borderline significant (p = 0.102) modifying effects of gender on the radiation dose trend, but no significant modifying effects of age at time of accident, or age at screening as modifiers of dose response (p>0.2).ConclusionsIn summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters.     

Impact of coronavirus disease 2019 on lung cancer patients: A meta-analysis

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic poses a great challenge to the treatment of lung cancer patients.Materials and methodsThe PubMed, Embase, and Web of Science databases were searched for studies published before March 15, 2022, and Stata 14.0 software was used to perform a meta-analysis with a random-effects model. The odds ratio (OR) along with the corresponding 95% confidence interval (CI) was reported.ResultsOur meta-analysis included 80 articles with 318,352 patients involved. The proportion of lung cancer patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 2.4% (95% CI: 0.02–0.03) prior to the Omicron variant outbreak. Among COVID-19 patients, those with lung cancer showed a higher mortality rate than those with other types of malignant solid tumors (OR = 1.82, 95% CI: 1.61–2.06) and non-cancer patients (OR = 4.67, 95% CI: 3.61–6.05); however, no significant difference was observed in the mortality rate between patients with lung cancer and those with hematologic malignancies (OR = 1.07, 95% CI: 0.85–1.33). SARS-CoV-2 infection significantly increased the mortality rate in lung cancer patients (OR = 8.94, 95% CI: 6.50–12.31). By contrast, the all-cause mortality rate in lung cancer patients (OR = 1.04, 95% CI: 0.69–1.57) and the proportion of patients diagnosed with advanced lung cancer (OR = 1.04, 95% CI: 0.85–1.27) did not significantly change before and after the pandemic.ConclusionsMore attention should be paid on improving the health of lung cancer patients during the COVID-19 pandemic.     

Image-guided volumetric arc radiotherapy of pancreatic cancer with simultaneous integrated boost: Optimization strategies and dosimetric results

PurposeTo introduce volumetric modulated arc therapy treatments (VMAT) with simultaneous integrated boost (SIB) for pancreatic cancer and describe dosimetric results on a large patient series.Methods and materials45 patients with pancreatic malignancies were treated with 18 MV single-arc VMAT. Image guidance was performed with daily online kilo-volt cone-beam computed tomography (CBCT). The conformity index (CI) and homogeneity index (HI) to the target volumes, PTV_45Gy and PTV_54Gy, and dose–volume indices to OARs from the QUANTEC task group were reported. The risk of clinical nephritis was evaluated using normal tissue complication probability (NTCP). Treatments were verified in-phantom with the Delta4 system.ResultsAverage CI was 1.06 with 95% confidence intervals (95% CI) of 0.97–1.22 for PTV_45Gy and 1.17 (0.66–1.61) for PTV_54Gy. HI of PTV_54Gy was 1.06 (1.04–1.10). OAR constraints were achieved in all patients, except for kidneys V_12Gy of 48 (35.4–72.3)%. NTCP of the kidneys was 0.98 (0.6–1.7)%. Kidneys V_12Gy and V_20Gy were inversely related to PTV_54Gy CI and maximum dose. All in-phantom tests had gamma pass rates exceeding 95% with global 3% dose difference and 3 mm distance to agreement. Patient shifts measured with CBCT had 95% CI of −0.8, +0.8 in the RL, −0.7, +0.8 in the SI, and −0.8, +0.7 cm in the AP directions.ConclusionsDosimetric results of VMAT were excellent on PTVs and organs at risk. The kidneys represent the dose-limiting organ at risk for this technique. NTCP indicates that this technique is safe from radiation-induced side effects to the kidneys.     

Dosimetric comparison of RapidPlan and manually optimized plans in volumetric modulated arc therapy for prostate cancer

PurposeThis study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer.MethodsWe used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D_95%, and D_2% to planning target volume (PTV), mean dose, V_50Gy, V_70Gy, V_75Gy, and V_78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity.ResultsRP and CMO values for PTV D_95%, PTV D_2%, HI, and CN were significantly similar (p < 0.05 for all). RP mean dose, V_50Gy, and V_70Gy to rectum were superior or comparable to CMO values; RP V_75Gy and V_78Gy were higher than in CMO plans (p < 0.05). RP bladder dose-volume parameter values (except V_78Gy) were lower than in CMO plans (p < 0.05). MU values were RP: 730 ± 55 MU and CMO: 580 ± 37 MU (p < 0.05); and MLC sequence complexity scores were RP: 0.25 ± 0.02 and CMO: 0.35 ± 0.03 (p < 0.05).ConclusionsRP plans created by a single optimization were clinically acceptable in VMAT for patient with prostate cancer. Our simple model could reduce optimization time, independently of planner’s skill and knowledge.     

Type 2 diabetes,obesity, and breast cancer risk among Japanese women of the atomic bomb survivor cohort

BackgroundMuch less is known about diabetes than obesity as a predictor of breast cancer incidence and most previous studies have been conducted in white populations. Therefore, this project within the Radiation Effects Research Foundation’s cohort of Japanese atomic bomb survivors aimed to determine the independent contributions of obesity and diabetes to develop breast cancer.MethodsAfter excluding women with unknown A-bomb radiation dose, a radiation dose of ≥100 mGy, a pre-existing history of breast cancer, and missing body mass index (BMI), the analysis included 29,818 women. Breast cancer status and deaths until 2009 were identified from cancer registries and vital records. Cox regression with age as the time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BMI and diabetes status as time-varying exposures alone and in combination while adjusting for known confounders.ResultsDiabetes prevalence increased from 2.6% to 5.3% and 7.5% from the first to the second and third data collection. During 27.6 ± 12.2 years of follow-up, 703 women had developed breast cancer (mean age of 66.0 ± 12.9 years) and 31 (4.4%) had been diagnosed with diabetes. A diagnosis of diabetes was not significantly associated with breast cancer incidence without (HR 1.12, 95% CI 0.77–1.64) and with BMI (HR 1.01, 95% CI 0.69–1.49) as a covariate. The respective HRs for overweight and obesity were 1.61 (95% CI 1.34–1.93) and 2.04 (95% CI 1.40–2.97).ConclusionsAmong a long-time Japanese cohort, excess body weight but not a diabetes diagnosis was significantly associated with breast cancer risk.     

Vaccination against SARS-CoV-2 and risk of hospital admission and death among infected cancer patients: A population-based study in northern Italy

BackgroundThe risks of hospital admission for COVID-19-related conditions and all-cause death of SARS-CoV-2 infected cancer patients were investigated according to vaccination status.MethodsA population-based cohort study was carried out on 9754 infected cancer patients enrolled from January 1, 2021 to June 30, 2022. Subdistribution hazard ratio (SHRs) or hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for sex, age, comorbidity index, and time since cancer incidence, were computed to assess the risk of COVID-19 hospital admission or death of unvaccinated vs. patients with at least one dose of vaccine (i.e., vaccinated).Results2485 unvaccinated patients (25.5 %) were at a 2.57 elevated risk of hospital admission (95 % CI: 2.13–2.87) and at a 3.50 elevated risk of death (95 % CI: 3.19–3.85), as compared to vaccinated patients. Significantly elevated hospitalizations and death risks emerged for both sexes, across all age groups and time elapsed since cancer diagnosis. For unvaccinated patients, SHRs for hospitalization were particularly elevated in those with solid tumors (SHR = 2.69 vs. 1.66 in patients with hematologic tumors) while HRs for the risk of death were homogeneously distributed. As compared to boosted patients, SHRs for hospitalization and HRs for death increased with decreasing number of doses.ConclusionsStudy findings stress the importance of SARS-CoV-2 vaccines to reduce hospital admission and death risk in cancer patients.     

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

BackgroundA recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients.MethodsNewly diagnosed [2009–2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders.Results1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR = 0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR = 0.88, 95% CI, 0.79, 0.99).ConclusionsIn this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis.     

Effects of lung tissue characterization in radiotherapy of breast cancer under deep inspiration breath hold when using Monte Carlo dosimetry

PurposeTo investigate the sensitivity of Monte Carlo (MC) calculated lung dose distributions to lung tissue characterization in external beam radiotherapy of breast cancer under Deep Inspiration Breath Hold (DIBH).MethodsEGSnrc based MC software was employed. Mean lung densities for one hundred patients were analysed. CT number frequency and clinical dose distributions were calculated for 15 patients with mean lung density below 0.14 g/cm³. Lung volume with a pre-defined CT numbers was also considered. Lung tissue was characterized by applying different CT calibrations in the low-density region and air-lung tissue thresholds. Dose impact was estimated by Dose Volume Histogram (DVH) parameters.ResultsMean lung densities below 0.14 g/cm³ were found in 10% of the patients. CT numbers below −960 HU dominated the CT frequency distributions with a high rate of CT numbers at −990 HU. Mass density conversion approach influenced the DVH shape. V_4Gy and V_8Gy varied by 7% and 5% for the selected patients and by 9% and 3.5% for the pre-defined lung volume. V_16Gy and V_20Gy, were within 2.5%. Regions above 20 Gy were affected. Variations in air- lung tissue differentiation resulted in DVH parameters within 1%. Threshold at −990 HU was confirmed by the CT number frequency distributions.ConclusionsLung dose distributions were more sensitive to variations in the CT calibration curve below lung (inhale) density than to air-lung tissue differentiation. Low dose regions were mostly affected. The dosimetry effects were found to be potentially important to 10% of the patients treated under DIBH.     

Lithuanian cohort of Chernobyl cleanup workers: Cancer incidence follow-up 1986–2012

BackgroundCancer risks following radiation exposure in adulthood after Chernobyl are less studied compared to those after exposure in childhood. We aimed to evaluate cancer risk in the Lithuanian cohort of Chernobyl cleanup workers 26 years after their exposure in Chernobyl.MethodsStudy population (6707 men) was followed for cancer incidence upon return from Chernobyl till the end of 2012 by linkage procedure with the Lithuanian Cancer Registry and for migration and death – with Central Population Registry. The site-specific cancer risk in the cohort was estimated by calculating the standardised incidence ratio (SIR) with 95 % confidence interval (CI).ResultsA total of 596 cancer cases was observed in the cohort, against 584 expected (SIR 1.02; 95 % CI 0.94, 1.11). Only incidence of mouth and pharynx cancers was increased compared to the expected (SIR 1.41; 95 % CI 1.07, 1.86). Nevertheless, an increased risk of thyroid cancer was observed among cleanup workers who were younger than 30 years when entering the Chernobyl zone (SIR 2.90; 95 % CI 1.09, 7.72), whose radiation dose was above 100 milisievert (mSv) (SIR 3.13; 95 % CI 1.30, 7.52) and who had shorter duration of stay (SIR 2.30; 95 % CI 1.03, 5.13).ConclusionsOur findings are consistent with those observed in other cohorts of workers, namely, the increased risk of cancer sites related to behavioural factors. The increased risk of thyroid cancer among cleanup workers who were younger than 30 years when entering Chernobyl and whose radiation dose was above 100 mSv cannot exclude the association with the radiation exposure in Chernobyl.     

Colorectal cancer ascertainment through cancer registries,hospital episode statistics,and self-reporting compared to confirmation by clinician: A cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

BackgroundElectronic health records are frequently used for cancer epidemiology. We report on their quality for ascertaining colorectal cancer (CRC) in UK women.MethodsPopulation-based, retrospective cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Postmenopausal women aged 50–74 who were diagnosed with CRC during 2001–11 following randomisation to the UKCTOCS were identified and their diagnosis confirmed with their treating clinician. The sensitivity and positive predictive value (PPV) of cancer and death registries, hospital episode statistics, and self-reporting were calculated by pairwise comparisons to the treating clinician’s confirmation, while specificity and negative predictive value were estimated relative to expected cases.ResultsNotification of CRC events were received for 1,085 women as of 24 May 2011. Responses were received from 61% (660/1,085) of clinicians contacted. Nineteen women were excluded (18 no diagnosis date, one diagnosed after cut-off). Of the 641 eligible, 514 had CRC, 24 had a benign polyp, and 103 had neither diagnosis. The sensitivity of cancer registrations at one- and six-years post-diagnosis was 92 (95% CI 90–94) and 99% (97–100), respectively, with a PPV of 95% (95% CI 92/93–97). The sensitivity & PPV of cancer registrations (at one-year post-diagnosis) & hospital episode statistics combined were 98 (96–99) and 92% (89–94), respectively.ConclusionsCancer and death registrations in the UK are a reliable resource for CRC ascertainment in women. Hospital episode statistics can supplement delays in cancer registration. Self-reporting seems less reliable.     

Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer

BackgroundPrecise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial.MethodsOur trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N = 442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms.ResultsOverdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14–1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95%CI 0.82–1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (κ = 0.88) in the SA and 95.4% (κ = 0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80–1.06).ConclusionsA small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling.     

The effect of silica exposure on the risk of lung cancer: A dose-response meta-analysis

BackgroundThe relationship between silica and the risk of developing lung cancer has been established in previous literature, but how much the level of exposure to silica can increase the risk of lung cancer is a question that has been addressed in this review.MethodsThree electronic databases, including MEDLINE, Scopus, and Web of Science were searched for relevant literature. For the dose-response relationship between exposure to silica and developing lung cancer, we performed a meta-analysis using the random-effects model. For each level of exposure, we calculated the overall risk ratio (RR) with 95% confidence intervals (CI).ResultsNineteen studies were included in the meta-analysis. There was a positive and significant increasing dose-response trend between silica exposure and the risk of developing lung cancer as follows: < 0.50 mg/m³ 1.14 (95% CI: 1.05, 1.23; I² = 79%), 0.50–0.99 mg/m³ 1.34 (95% CI: 1.05, 171; I² = 45%), 1.00–1.99 mg/m³ 1.14 (95% CI: 1.00, 1.30; I² = 70%), 2.00–2.99 mg/m³ 1.47 (95% CI: 1.05, 2.06; I² = 57%), 3.00–3.99 mg/m³ 1.44 (95% CI: 0.99, 2.11; I² = 58%), and ≥ 4.00 mg/m³ 1.64 (95% CI: 1.20, 2.24; I² = 88%). The heterogeneity across studies was mild to moderate.ConclusionsThe presence of a dose-response relationship favors the causal relationship between exposure to silica and developing lung cancer.     

Relative rates of cancers and deaths in Australian communities with PFAS environmental contamination associated with firefighting foams: A cohort study using linked data

BackgroundPer- and polyfluoroalkyl substances (PFAS) are environmental contaminants that are potentially harmful to health. We examined if rates of selected cancers and causes of deaths were elevated in three Australian communities with local environmental contamination caused by firefighting foams containing PFAS. The affected Australian communities were Katherine in Northern Territory, Oakey in Queensland and Williamtown in New South Wales.MethodsAll residents identified in the Medicare Enrolment File (1983–2019)—a consumer directory for Australia’s universal healthcare—who ever lived in an exposure area (Katherine, Oakey and Williamtown), and a sample of those who ever lived in selected comparison areas, were linked to the Australian Cancer Database (1982–2017) and National Death Index (1980–2019). We estimated standardised incidence ratios (SIRs) for 23 cancer outcomes, four causes of death and three control outcomes, adjusting for sex, age and calendar time of diagnosis.FindingsWe observed higher rates of prostate cancer (SIR=1·76, 95 % confidence interval (CI) 1·36–2·24) in Katherine; laryngeal cancer (SIR=2·71, 95 % CI 1·30–4·98), kidney cancer (SIR=1·82, 95 % CI 1·04–2·96) and coronary heart disease (CHD) mortality (SIR=1·81, 95 % CI 1·46–2·33) in Oakey; and lung cancer (SIR=1·83, 95 % CI 1·39–2·38) and CHD mortality (SIR=1·22, 95 % CI 1·01–1·47) in Williamtown. We also saw elevated SIRs for control outcomes. SIRs for all other outcomes and overall cancer were similar across exposure and comparison areas.InterpretationThere was limited evidence to support an association between living in a PFAS exposure area and risks of cancers or cause-specific deaths.     

Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort

BackgroundMammographic density is a known heritable risk factor for breast cancer, but reports how tumor characteristics and family history may modify this association are inconsistent.MethodsDense and total breast areas were assessed using Cumulus™ from pre-diagnostic mammograms for 820 invasive breast cancer cases and 820 matched controls nested within the French E3N cohort study. To allow comparisons across models, percent mammographic density (PMD) was standardized to the distribution of the controls. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer risk for mammographic density were estimated by conditional logistic regression while adjusting for age and body mass index. Heterogeneity according to tumor characteristic and family history was assessed using stratified analyses.ResultsOverall, the OR per 1 SD for PMD was 1.50 (95% CI, 1.33–1.69). No evidence for significant heterogeneity by tumor size, lymph node status, grade, and hormone receptor status (estrogen, progesterone, and HER2) was detected. However, the association of PMD was stronger for women reporting a family history of breast cancer (OR_1SD = 2.25; 95% CI, 1.67–3.04) than in women reporting none (OR_1SD = 1.41; 95% CI, 1.24–1.60; p_{heterogeneity} = 0.002). Similarly, effect modification by FHBC was observed using categories of PMD (p_{heterogeneity} = 0.02) with respective ORs of 15.16 (95% CI, 4.23–54.28) vs. 3.14 (95% CI, 1.89–5.22) for ≥50% vs. <10% PMD.ConclusionsThe stronger association between mammographic density and breast cancer risk with a family history supports the hypothesis of shared genetic factors responsible for familial aggregation of breast cancer and the heritable component of mammographic density.