Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium

Background In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. Methods We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3–19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. Results 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03–1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01–1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03–1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12–1.63). Conclusions Higher childhood BMI was independently associated with increased overall cancer mortality.

Incident cardiovascular events among healthy subjects are associated with increased risk of subsequent cancer diagnosis

Introduction While Cardiovascular disease (CVD) and cancer share common risk factors, data on the temporal association between the occurrence of CVD and cancer is limited. Purpose This study investigated the association between incident CVD events future cancer among apparently healthy subjects. Methods We evaluated asymptomatic self-referred adults who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention, or stroke. Study endpoint was the development of cancer during follow up. Cancer and mortality data were available for all subjects from national registries. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event. Results Final study population included 26,574 subjects. Median age was 46 years (Interquartile range [IQR] 40–53) and 69% were men. During median follow up time of 10 years (IQR 3–16) 2,463 (9%) subjects developed CVD, 2,040 (8%) developed cancer and 869 (3%) died. Most common cancer types were prostate among men (N=406, 2.2%) and breast among women (N=283, 3.4%). Compared with patients who were free of CVD and cancer during follow up, risk of death was 5, 34 and 54 times higher for patients who developed CVD event, cancer, or both during follow up, respectively (p <.001 for all). Time dependent survival analysis showed that subjects who developed CVD during follow up were 50% more likely to develop cancer in a univariate model (95% Confidence Interval [CI] 1.3–1.7, p<.001). Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in younger subjects (≤52 years; N=19,052) incident CVD was associated with a significant 30% increased risk of subsequent cancer diagnosis (95% CI 1.03–1.67, p=.027) while in older subjects incident CVD was not associated with increased risk of cancer in the multivariable model (p for interaction =.018). Conclusion Incident CVD is independently associated with increased risk of subsequent cancer diagnosis among young adults. Active cancer surveillance should be considered among young patients recovering from a CVD event. FUNDunding Acknowledgement Type of funding sources: None.

Hormone replacement therapy and cancer survival: a longitudinal cohort study: protocol paper

IntroductionHormone replacement therapy (HRT) can help women experiencing menopausal symptoms, but usage has declined due to uncertainty around risks of cancer and some cardiovascular diseases (CVD). Moreover, improved cancer survival rates mean that more women who survive cancer go on to experience menopausal symptoms. Understanding these relationships is important so that women and their clinicians can make informed decisions around the risks and benefits of HRT. This study’s primary aim is to determine the association between HRT use after cancer diagnosis and the risk of cancer-specific mortality. The secondary aims are to investigate the risks of HRT on subsequent cancer, all-cause mortality and CVD.Methods and analysisWe will conduct a population-based longitudinal cohort study of 18–79 year-old women diagnosed with cancer between 1998 and 2020, using the QResearch database. The main exposure is HRT use, categorised based on compound, dose and route of administration, and modelled as a time-varying covariate. Analysis of HRT use precancer and postcancer diagnosis will be conducted separately. The primary outcome is cancer-specific mortality, which will be stratified by cancer site. Secondary outcomes include subsequent cancer diagnosis, CVD (including venous thrombo-embolism) and all-cause mortality. Adjustment will be made for key confounders such as age, body mass index, ethnicity, deprivation index, comorbidities, and cancer grade, stage and treatment. Statistical analysis will include descriptive statistics and Cox proportional hazards models to calculate HRs and 95% CIs.Ethics and disseminationEthical approval for this project was obtained from the QResearch Scientific Committee (Ref: OX24, project title ‘Use of hormone replacement therapy and survival from cancer’). This project has been, and will continue to be, supported by patient and public involvement panels. We intend to the submit the findings for peer-reviewed publication in an academic journal and disseminate them to the public through Cancer Research UK.

Incident cardiovascular events and risk of subsequent cancer diagnosis

Background Cardiovascular disease (CVD) and cancer share common risk factors. This study investigated the association of CVD diagnosis and the risk of future cancer. Methods We evaluated asymptomatic self-referred adults aged 40–79 years who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention or stroke. Cancer and mortality data were available for all subjects from national registries. Primary end-point was development of cancer during follow up. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event. Results Final study population included 15,486 subjects. Median age was 50 years (Interquartile range [IQR] 44–55) and 72% were men. During median follow up time of 11 years (IQR 6–15) 1,028 (7%) subjects developed CVD, 1,281 (8%) developed cancer and 499 (3%) died. Most common cancer types were prostate among men (N=277, 1.8%) and breast among women (N=187, 1.2%). Time dependent survival analysis showed that subjects who developed CVD during follow up were 60% more likely to develop cancer (95% Confidence Interval [CI] 1.3–1.95, p<0.001). However, after adjustment for known predictors of cancer, the association of incident CVD with cancer diagnosis was no longer significant (p=0.21). Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in younger subjects (<50 years; N=7,649) incident CVD was associated with a significant 2 fold increased risk of subsequent cancer diagnosis (95% CI 1.2–3.6, p=0.014) while in older subjects incident CVD was not associated with increased risk of cancer in the multivariable model (p for interaction =0.035; Figure 1). Conclusions Incident CVD is independently associated with 2-fold increased risk of subsequent cancer diagnosis among young adults. Our analysis underscores the importance of cancer surveillance among young patients following a CVD event. Figure 1 Funding Acknowledgement Type of funding source: None