Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that ...inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study.
Using linked administrative data, a population-based cohort of 3,844 Australian women age 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for survival outcomes. The average treatment effect of selective BB (SBB) and nonselective BB (NSBB) supply at the time of surgery on survival was estimated from a causal inference perspective using covariate-balanced inverse probability of treatment weights with flexible parametric survival models that allowed for time-varying survival effects.
Around the time of surgery, 560 (14.5%) women were supplied a SBB and 67 (1.7%) were supplied a NSBB. At 2 years postsurgery, the survival proportion was 80% (95% CI, 68 to 88) for women dispensed NSBBs at surgery compared with 69% (95% CI, 67 to 70) for women not supplied NSBBs. The survival advantage appeared to extend to at least 8 years postsurgery. No association was observed for women dispensed a SBB around the time of surgery.
Perioperative supply of NSBBs appeared to confer a survival advantage for women age over 50 years with a history of cardiovascular conditions. Long-term clinical trials are required to confirm these findings.
Hysterectomy is one of the most commonly performed gynecologic surgeries, with an estimated 30% of women in Australia undergoing the procedure by age of 70 years. In the United States, about 45% of ...women undergo hysterectomy in their lifetime. Some studies have suggested that this procedure increases the risk of premature mortality. With many women making the decision to undergo hysterectomy for a benign indication each year, additional research is needed to clarify whether there are long-term health consequences of hysterectomy.
This study aimed to examine the association between hysterectomy for benign indications, with or without removal of the ovaries, and cause-specific and all-cause mortality.
Our cohort of 666,588 women comprised the female population of Western Australia with linked hospital and health records from 1970 to 2015. Cox regression models were used to assess the association between hysterectomy and all-cause, cardiovascular disease, cancer, and other mortality by oophorectomy type (categorized as none, unilateral, and bilateral), with no hysterectomy or oophorectomy as the reference group. We repeated these analyses using hysterectomy without oophorectomy as the reference group. We also investigated whether associations varied by age at the time of surgery, although small sample size precluded this analysis in women who underwent hysterectomy with unilateral salpingo-oophorectomy.
In our main analysis, women who underwent hysterectomy or oophorectomy as part of cancer treatment were retained in the analysis and considered unexposed to that surgery. For a sensitivity analysis, we censored procedures performed for cancer.
Compared with no surgery, hysterectomy without oophorectomy before 35 years was associated with an increase in all-cause mortality (hazard ratio, 1.29; 95% confidence interval, 1.19–1.40); for surgery after 35 years of age, there was an inverse association (35–44 years: hazard ratio, 0.93; 95% confidence interval, 0.89–0.97). Similarly, hysterectomy with bilateral salpingo-oophorectomy before 45 years of age was associated with increased all-cause mortality (35–44 years: hazard ratio, 1.15; 95% confidence interval, 1.04–1.27), but decreased mortality rates after 45 years of age. In our sensitivity analysis, censoring gynecologic surgeries for cancer resulted in many cancer-related deaths being excluded for women who did not have surgery for benign indications and thus increased the hazard ratios for the associations between both hysterectomy without oophorectomy and hysterectomy with bilateral salpingo-oophorectomy and risk of all-cause and cancer-specific mortality. The sensitivity analysis therefore potentially biased the results in favor of no surgery.
Among women having surgery for benign indications, hysterectomy without oophorectomy performed before 35 years of age and hysterectomy with bilateral salpingo-oophorectomy performed before 45 years of age were associated with an increase in all-cause mortality. These procedures are not associated with poorer long-term survival when performed at older ages.
Objective:
People with severe mental illness have similar cancer incidence, but higher mortality than the general population. Participation in cancer screening may be a contributing factor but ...existing studies are conflicting. The aim of this study was to investigate the frequency of colorectal, prostate and cervical cancer screening among people with and without severe mental illness in Australia, who have access to universal health care.
Methods:
We followed three cohorts using de-identified data from a random 10% sample of people registered for Australia’s universal health care system: those aged 50–69 years (n = 760,058) for colorectal cancer screening; women aged 18–69 years (n = 918,140) for cervical cancer screening and men aged 50–69 years (n = 380,238) for prostate cancer screening. We used Poisson regression to estimate incidence rate ratios and 95% confidence intervals for the association between severe mental illness and rates of faecal occult blood testing, pap smears and prostate-specific antigen testing.
Results:
Having severe mental illness was associated with a 17% reduction in rates of pap smear (incidence rate ratio = 0.83, 95% confidence interval: 0.82–0.84) and prostate-specific antigen testing (incidence rate ratio = 0.83, 95% confidence interval: 0.81–0.85), compared to the general population. By contrast, incidence rates of faecal occult blood testing were only lower in people with severe mental illness among the participants who visited their general practitioner less than an average of five times per year (incidence rate ratio = 0.83, 95% confidence interval = 0.73, 0.94).
Conclusion:
Our results suggest that differences in screening frequency may explain some of the mismatch between cancer incidence and mortality in people with severe mental illness and indicate that action is required to improve preventive screening in this very disadvantaged group.
This study aimed to investigate the associations between hysterectomy for benign indications and risk of breast, colorectal, kidney, and thyroid cancer, and to explore whether these associations are ...modified by removal of ovaries at the time of surgery or by age at surgery.
We conducted a retrospective cohort study of the female population of Western Australia (
= 839,332) linking data from electoral, hospital, births, deaths, and cancer records. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the associations between hysterectomy and diagnosis of breast, colorectal, kidney, and thyroid cancers.
Compared with no surgery, hysterectomy without oophorectomy (hysterectomy) and hysterectomy with bilateral salpingo-oophorectomy (hysterectomy-BSO) were associated with higher risk of kidney cancer (HR, 1.32; 95% CI, 1.11-1.56 and HR, 1.29; 95% CI, 0.96-1.73, respectively). Hysterectomy, but not hysterectomy-BSO, was related to higher risk of thyroid cancer (HR, 1.38; 95% CI, 1.19-1.60). In contrast, hysterectomy (HR, 0.94; 95% CI, 0.90-0.98) and hysterectomy-BSO (HR, 0.92; 95% CI, 0.85-1.00) were associated with lower risk of breast cancer. We found no association between hysterectomy status and colorectal cancer.
The associations between hysterectomy and cancer varied by cancer type with increased risks for thyroid and kidney cancer, decreased risk for breast cancer, and no association for colorectal cancer.
As breast, colorectal, and gynecologic cancers comprise a sizeable proportion of all cancers in women, our results suggest that hysterectomy is unlikely to increase overall cancer risk; however, further research to understand the higher risk of thyroid and kidney cancer is warranted.
Abstract
Background
There are few readily modifiable risk factors for epithelial ovarian cancer; preclinical studies suggest bisphosphonates could have chemopreventive actions. Our study aimed to ...assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype.
Methods
We conducted a case-control study nested within a large, linked administrative dataset including all Australian women enrolled for Medicare, Australia’s universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between July 1, 2004, and December 31, 2013 (n = 9367) and randomly selected up to 5 controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46 830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene, and other osteoporosis medicines (no nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression.
Results
Ever use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared with no use (OR = 0.81, 95% CI = 0.75 to 0.88). There was a reduced risk of endometrioid (OR = 0.51, 95% CI = 0.33 to 0.79) and serous histotypes (OR = 0.84, 95% CI = 0.75 to 0.93) but no association with the mucinous or clear cell histotypes.
Conclusion
Use of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.
Response to Lehrer and Rheinstein Tuesley, Karen M; Webb, Penelope M; Protani, Melinda M ...
JNCI : Journal of the National Cancer Institute,
10/2022, Letnik:
114, Številka:
10
Journal Article
Epithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed ...the associations between use of different antihypertensive medicines and risk of specific EOC histotypes.
Our nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes.
We found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82).
Our results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.
•Most antihypertensive medicines were not associated with ovarian cancer risk.•Use of calcium channel blockers were associated with decreased risk of serous ovarian cancers.•Thiazide/potassium-sparing diuretics doubled the risk of endometrioid ovarian cancer.
Background and Aim
People with new‐onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic ...cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new‐onset diabetes.
Methods
We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti‐diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3 years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2 months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer.
Results
Among 99 687 women aged ≥ 50 years with new‐onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3 years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta‐blockers, acid disorder drugs, and lipid‐modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%.
Conclusions
Our model doubled the PPV of pancreatic cancer in women with new‐onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.
Abstract
Background
Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, has a five-year survival of ∼45%, and very few established modifiable risk factors. Some evidence ...suggests that bisphosphonates could have chemopreventive benefits, but few epidemiological studies have investigated the association between bisphosphonate use and incidence of EOC.
Methods
We conducted a nested case-control study using linked administrative data. We identified 9,367 women over 50 years diagnosed with EOC (cases) from 2004 to 2013, and for each case identified five controls from the Australian Medicare Enrolment database matched by age, state, area of residence, and area-level socioeconomic disadvantage. We assessed the associations between bisphosphonate use using dispensed prescription data (ever use, duration and dose) and EOC (overall, by histotype), adjusting for comorbidities and MHT use. We conducted sensitivity analyses in women with complete ascertainment of dispensing claims and for residents of one Australian state that had linked with data linked to hospital procedures, including oophorectomy.
Results
Our analyses show an inverse association between bisphosphonate use and risk of EOC overall (OR = 0.81, 95%CI:0.75-0.88), and for endometrioid (OR = 0.51, 95%CI:0.33-0.79) and serous (OR = 0.84, 95%CI:0.75-0.93) histotypes. There was some evidence that higher dose and duration were associated with a greater reduction in risk. Results from sensitivity analyses were not appreciably different.
Conclusions
Bisphosphonate use was associated with lower risk of EOC, suggesting bisphosphonates may reduce risk of ovarian cancer development.
Key messages
Bisphosphonates may protect against development of serous and endometrioid ovarian cancers.
Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between ...diabetes deterioration and pancreatic cancer has received little attention.
We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI).
We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years.
Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.
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