There is some evidence that place of residence is associated with cancer survival, but the findings are inconsistent, and the underlying mechanisms by which residential location might affect survival ...are not well understood. We conducted a systematic review of observational studies investigating the association of rural versus urban residence with cancer survival in high‐income countries. We searched the Ovid Medline, EMBASE, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases up to May 31, 2016. Forty‐five studies published between 1984 and 2016 were included. We extracted unadjusted and adjusted relative risk estimates with the corresponding 95% confidence intervals. Most studies reported worse survival for cancer patients living in rural areas than those in urban regions. The most consistent evidence, observed across several studies, was for colorectal, lung, and prostate cancer. Of the included studies, 18 did not account for socio‐economic position. Lower survival for more disadvantaged patients is well documented; therefore, it could be beneficial for future research to take socio‐economic factors into consideration when assessing rural/urban differences in cancer survival. Some studies cited differential stage at diagnosis and treatment modalities as major contributing factors to regional inequalities in cancer survival. Further research is needed to disentangle the mediating effects of these factors, which may help to establish effective interventions to improve survival for patients living outside major cities.
A systematic review of 45 observational studies reveals that cancer patients living in rural areas generally have worse survival than their urban counterparts. The most consistent evidence, observed across several studies, is for colorectal, lung, and prostate cancer. Identifying the underlying mechanisms of survival disadvantage for rural cancer patients may help to establish effective interventions and improve survival.
Background:
There is strong and well-documented evidence that socio-economic inequality in cancer survival exists within and between countries, but the underlying causes of these differences are not ...well understood.
Methods:
We systematically searched the Ovid Medline, EMBASE, and CINAHL databases up to 31 May 2020. Observational studies exploring pathways by which socio-economic position (SEP) might causally influence cancer survival were included.
Results:
We found 74 eligible articles published between 2005 and 2020. Cancer stage, other tumor characteristics, health-related lifestyle behaviors, co-morbidities and treatment were reported as key contributing factors, although the potential mediating effect of these factors varied across cancer sites. For common cancers such as breast and prostate cancer, stage of disease was generally cited as the primary explanatory factor, while co-morbid conditions and treatment were also reported to contribute to lower survival for more disadvantaged cases. In contrast, for colorectal cancer, most studies found that stage did not explain the observed differences in survival by SEP. For lung cancer, inequalities in survival appear to be partly explained by receipt of treatment and co-morbidities.
Conclusions:
Most studies compared regression models with and without adjusting for potential mediators; this method has several limitations in the presence of multiple mediators that could result in biased estimates of mediating effects and invalid conclusions. It is therefore essential that future studies apply modern methods of causal mediation analysis to accurately estimate the contribution of potential explanatory factors for these inequalities, which may translate into effective interventions to improve survival for disadvantaged cancer patients.
Despite overall improvements in cancer survival due to earlier diagnosis and better treatment, socio-economically disadvantaged people have lower cancer survival than more advantaged people. We aimed ...to examine differences in cancer survival by area-level socio-economic disadvantage in Victoria, Australia and assess whether these inequalities varied by year of diagnosis, age at diagnosis, time since diagnosis and sex. Cases diagnosed with a first primary cancer in 2001-2015 were identified using the Victorian Cancer Registry and followed to the end of 2016. Five-year net survival and the excess risk of death due to a cancer diagnosis were estimated. People living in more disadvantaged areas had lower five-year survival than residents of less disadvantaged regions for 21 of 29 cancer types: head and neck, oesophagus, stomach, colorectum, anus/anal canal, liver, gallbladder/biliary tract, pancreas, lung, melanoma, connective/soft tissue, female breast, ovary, prostate, kidney, bladder, brain and central nervous system, unknown primary, non-Hodgkin lymphoma, multiple myeloma and leukemia. The observed lower survival in more deprived regions persisted over time, except head and neck cancer, for which the gap in survival has widened. Socio-economic inequalities in survival decreased with increasing age at diagnosis for cancers of connective/soft tissue, bladder and unknown primary. For colorectal cancer, the observed survival disadvantage in lower socio-economic regions was greater for men than for women, while for brain and central nervous system tumours, it was larger for women. Cancer survival is generally lower for residents of more socio-economically disadvantaged areas. Identifying the underlying reasons for these inequalities is important and may help to identify effective interventions to increase survival for underprivileged cancer patients.
The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them “age acceleration.” We aimed to assess the ...associations of age acceleration with risk of and survival from seven common cancers. Seven case–control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer and B‐cell lymphoma nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450 K Beadchip assay with cancer risk (N = 3,216 cases) and survival (N = 1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five‐year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B‐cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five‐year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15–30% for the fourth versus first quartile of age acceleration. DNA methylation‐based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors.
What's new?
Aging is associated with profound changes in DNA methylation levels. These can be used to build accurate age predictors (“epigenetic clocks”) that deviate from chronological age by only a few years, a phenomenon named “age acceleration”. In this study of seven types of cancer, the authors found that age acceleration was associated with both increased cancer risk and decreased cancer survival, independently of major health risk factors. These results support the usefulness of methylation markers of biological aging as a tool to predict health outcomes and may provide valuable insight into the relationship between aging and cancer.
Increasing multidrug resistance in Gram-negative bacteria, in particular
Pseudomonas aeruginosa, Acinetobacter baumannii, and
Klebsiella pneumoniae, presents a critical problem. Limited therapeutic ...options have forced infectious disease clinicians and microbiologists to reappraise the clinical application of colistin, a polymyxin antibiotic discovered more than 50 years ago. We summarise recent progress in understanding the complex chemistry, pharmacokinetics, and pharmacodynamics of colistin, the interplay between these three aspects, and their effect on the clinical use of this important antibiotic. Recent clinical findings are reviewed, focusing on evaluation of efficacy, emerging resistance, potential toxicities, and combination therapy. In the battle against rapidly emerging bacterial resistance we can no longer rely entirely on the discovery of new antibiotics; we must also pursue rational approaches to the use of older antibiotics such as colistin.
To determine whether recommended amounts of leisure-time physical activity (ie, 7.5-15 metabolic equivalent task MET hours/week) are associated with lower cancer risk, describe the shape of the ...dose-response relationship, and explore associations with moderate- and vigorous-intensity physical activity.
Data from 9 prospective cohorts with self-reported leisure-time physical activity and follow-up for cancer incidence were pooled. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% CIs of the relationships between physical activity with incidence of 15 types of cancer. Dose-response relationships were modeled with restricted cubic spline functions that compared 7.5, 15.0, 22.5, and 30.0 MET hours/week to no leisure-time physical activity, and statistically significant associations were determined using tests for trend (
< .05) and 95% CIs (< 1.0).
A total of 755,459 participants (median age, 62 years range, 32-91 years; 53% female) were followed for 10.1 years, and 50,620 incident cancers accrued. Engagement in recommended amounts of activity (7.5-15 MET hours/week) was associated with a statistically significant lower risk of 7 of the 15 cancer types studied, including colon (8%-14% lower risk in men), breast (6%-10% lower risk), endometrial (10%-18% lower risk), kidney (11%-17% lower risk), myeloma (14%-19% lower risk), liver (18%-27% lower risk), and non-Hodgkin lymphoma (11%-18% lower risk in women). The dose response was linear in shape for half of the associations and nonlinear for the others. Results for moderate- and vigorous-intensity leisure-time physical activity were mixed. Adjustment for body mass index eliminated the association with endometrial cancer but had limited effect on other cancer types.
Health care providers, fitness professionals, and public health practitioners should encourage adults to adopt and maintain physical activity at recommended levels to lower risks of multiple cancers.
Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by ...performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes. Results Data from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P < .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P < .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); > 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS ( P = .043), but not for the DDFS and OS end points. Conclusion In this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors.
Pathogenic mutations in BRCA1 and BRCA2 are associated with high risks of breast and ovarian cancer. However, penetrance estimates for mutation carriers have been found to vary substantially between ...studies, and the observed differences in risk are consistent with the hypothesis that genetic and environmental factors modify cancer risks for women with these mutations. Direct evidence that this is the case has emerged in the past decade, through large-scale international collaborative efforts. Here, we describe the methodological challenges in the identification and characterisation of these risk-modifying factors, review the latest evidence on genetic and lifestyle/hormonal risk factors that modify breast and ovarian cancer risks for women with BRCA1 and BRCA2 mutations and outline the implications of these findings for cancer risk prediction. We also review the unresolved issues in this area of research and identify strategies of clinical implementation so that women with BRCA1 and BRCA2 mutations are no longer counselled on the basis of 'average' risk estimates.
Differences in cancer survival by sex Afshar, Nina; English, Dallas R.; Thursfield, Vicky ...
Cancer causes & control,
11/2018, Letnik:
29, Številka:
11
Journal Article
Recenzirano
Purpose
Few large-scale studies have investigated sex differences in cancer survival and little is known about their temporal and age-related patterns.
Methods
We used cancer registry data for first ...primary cancers diagnosed between 1982 and 2015 in Victoria, Australia. Cases were followed until the end of 2015 through linkage to death registries. Differences in survival were assessed for 25 cancers using the Pohar-Perme estimator of net survival and the excess mortality rate ratio (EMRR) adjusting for age and year of diagnosis.
Results
Five-year net survival for all cancers combined was lower for men (47.1%; 95% CI 46.9–47.4) than women (52.0%; 95% CI 51.7–52.3); EMRR 1.13 (95% CI 1.12–1.14;
p
< 0.001). A survival disadvantage for men was observed for 11 cancers: head and neck, esophagus, colorectum, pancreas, lung, bone, melanoma, mesothelioma, kidney, thyroid, and non-Hodgkin lymphoma. In contrast, women had lower survival from cancers of the bladder, renal pelvis, and ureter. For the majority of cancers with survival differences, the EMRR decreased with increasing age at diagnosis; for colorectal, esophageal, and kidney cancer, the EMRR increased with time since diagnosis.
Conclusion
Identifying the underlying reasons behind sex differences in cancer survival is necessary to address inequalities, which may improve outcomes for men and women.
The heterogeneity among colorectal tumors is probably due to differences in developmental pathways and might associate with patient survival times. We studied the relationship among markers of ...different subtypes of colorectal tumors and patient survival.
We pooled data from 7 observational studies, comprising 5010 patients with colorectal cancer. All the studies collected information on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in KRAS and BRAF in tumors. Tumors with complete marker data were classified as type 1 (MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 2 (not MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 3 (not MSI-high or CIMP, with pathogenic mutations in KRAS but not BRAF), type 4 (not MSI-high or CIMP, no pathogenic mutations in BRAF or KRAS), or type 5 (MSI-high, no CIMP, no pathogenic mutations in BRAF or KRAS). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations of these subtypes and tumor markers with disease-specific survival (DSS) and overall survival times, adjusting for age, sex, stage at diagnosis, and study population.
Patients with type 2 colorectal tumors had significantly shorter time of DSS than patients with type 4 tumors (HRDSS 1.66; 95% CI 1.33–2.07), regardless of sex, age, or stage at diagnosis. Patients without MSI-high tumors had significantly shorter time of DSS compared with patients with MSI-high tumors (HRDSS 0.42; 95% CI 0.27–0.64), regardless of other tumor markers or stage, or patient sex or age.
In a pooled analysis of data from 7 observational studies of patients with colorectal cancer, we found that tumor subtypes, defined by combinations of 4 common tumor markers, were associated with differences in survival time. Colorectal tumor subtypes might therefore be used in determining patients’ prognoses.
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