The discordant twin pair study design is powerful to control for familial confounding. We employed this approach to investigate the associations of smoking with several cancers. The NorTwinCan study ...combines data from the Danish, Finnish, Norwegian and Swedish twin and cancer registries. Follow-up started when smoking status was determined and ended at cancer diagnosis confirmed by information in the cancer registry, death or end of follow-up. We classified the participants as never (n = 59 093), former (n = 21 168) or current (n = 47 314) smokers. We pooled data from twin pairs where one co-twin was diagnosed with any of the following tobacco-related cancers: esophagus, kidney, larynx, liver, oral cavity, pancreas, pharynx or urinary bladder, while their co-twin had none of those. Lung cancer was included in further analysis. We used Cox regression allowing for pair-specific baseline functions to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). For tobacco-related cancer sites, we recorded 7379 cases during median 27 years of follow-up. The analyses based on individual twins showed that former (HR 1.31, 95% CI: 1.17-1.48) and current (HR 2.14 1.95-2.34) smokers are at increased risk to develop one of cancers listed above, compared to never smokers. Among 109 monozygotic twin pairs discordant for cancer and smoking, the HR was 1.85 (95% CI: 1.15-2.98) among current smokers and 1.69 (1.00-2.87) among former smokers when compared to their never smoking co-twin. Thus, associations of smoking with several cancers were replicated for discordant identical twin pairs. Analyses based on genetically informative data provide evidence consistent with smoking causing multiple cancers.
Abstract
Using Epstein-Barr virus (EBV)-based markers to screen populations at high risk for nasopharyngeal carcinoma (NPC) is an attractive preventive approach. Here, we develop a comprehensive risk ...score (CRS) that combines risk effects of EBV and human genetics for NPC risk stratification and validate this CRS within an independent, population-based dataset. Comparing the top decile with the bottom quintile of CRSs, the odds ratio of developing NPC is 21 (95% confidence interval: 12–37) in the validation dataset. When combining the top quintile of CRS with EBV serology tests currently used for NPC screening in southern China, the positive prediction value of screening increases from 4.70% (serology test alone) to 43.24% (CRS plus serology test). By identifying individuals at a monogenic level of NPC risk, this CRS approach provides opportunities for personalized risk prediction and population screening in endemic areas for the early diagnosis and secondary prevention of NPC.
In a mission that aims to improve cancer control throughout Europe, the European Academy of Cancer Sciences has defined two key indicators of progress: within one to two decades, overall ...cancer‐specific 10‐year survival should reach 75%, and in each country, overall cancer mortality rates should be convincingly declining. To lay the ground for assessment of progress and to promote cancer outcomes research in general, we have reviewed the most common population‐based measures of the cancer burden. We emphasize the complexities and complementary approaches to measure cancer survival and the novel opportunities for improved assessment of quality of life. We propose that: incidence and mortality rates are standardized to the European population; net survival is used as the measure of prognosis but with proper adjustments for confounding when temporal trends in overall cancer survival are assessed; and cancer‐specific quality of life is measured by a combination of existing questionnaires and utilizes emerging communication technologies. We conclude that all measures are important and that a meaningful interpretation also requires a deep understanding of the larger clinical and public health context.
This review defines the many measures used to quantify the burden of cancer, their pros, cons, and utility for different purposes. Recommendations are provided for the most informative measures and the methodologic challenges that need accommodation in assessing the Academy's goals. The needs and opportunities for development of and standardization of cancer‐specific quality of life assessments is also emphasized.
Abstract
STUDY QUESTION
Are parity and the timing of menarche associated with premature and early natural menopause?
SUMMARY ANSWER
Early menarche (≤11 years) is a risk factor for both premature ...menopause (final menstrual period, FMP <40 years) and early menopause (FMP 40–44 years), a risk that is amplified for nulliparous women.
WHAT IS KNOWN ALREADY
Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power.
STUDY DESIGN, SIZE, DURATION
This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40–44 years), 45–49 years, 50–51 years, 52–53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation.
MAIN RESULTS AND THE ROLE OF CHANCE
The median age at FMP was 50 years (interquartile range 48–53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12–13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53–2.12) and early menopause (1.31, 1.19–1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84–2.77) and early menopause (1.32, 1.09–1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04–7.87) and 2-fold increased risk of early menopause (2.16, 1.48–3.15) compared with women who had menarche at ≥12 years and two or more children.
LIMITATIONS, REASONS FOR CAUTION
Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause.
STUDY FUNDING/COMPETING INTEREST(S)
InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests.
Growing evidence suggests that obesity, an established cause of renal cell cancer (RCC), may also be associated with a better prognosis. To evaluate the association between RCC survival and obesity, ...we analyzed a large cohort of patients with RCC and undertook a meta‐analysis of the published evidence. We collected clinical and pathologic data from 1,543 patients who underwent nephrectomy for RCC between 1994 and 2008 with complete follow‐up through 2008. Patients were grouped according to BMI (kg/m2): underweight <18.5, normal weight 18.5 to <23, overweight 23 to <25 and obese ≥25. We estimated survival using the Kaplan–Meier method and Cox proportional hazard models to examine the impact of BMI on overall survival (OS) and cancer‐specific survival (CSS) with adjustment for covariates. We performed a meta‐analysis of BMI and OS, CSS and recurrence‐free survival (RFS) from all relevant studies using a random‐effects model. The 5‐year CSS increased from 76.1% in the lowest to 92.7% in the highest BMI category. A multivariate analysis showed higher OS hazard ratio (HR) = 0.45; 95% CI: 0.29–0.68) and CSS (HR = 0.47; 95% CI: 0.29–0.77 in obese patients than in normal weight patients. The meta‐analysis further corroborated that high BMI significantly improved OS (HR = 0.57; 95% CI: 0.43–0.76), CSS (HR = 0.59; 95% CI: 0.48–0.74) and RFS (HR = 0.49; 95% CI: 0.30–0.81). Our study shows that preoperative BMI is an independent prognostic indicator for survival among patients with RCC.
Enigmatic sex disparities in cancer incidence Edgren, Gustaf; Liang, Liming; Adami, Hans-Olov ...
European journal of epidemiology,
03/2012, Letnik:
27, Številka:
3
Journal Article
Recenzirano
In this study we aimed to identify cancers where there is a consistent sex disparity, with the goal of identifying unexplained sex disparities that may offer promising opportunities for etiologic ...research. Age- and sex-specific cancer incidence data from Cancer Incidence in Five Continents, provided by the International Agency for Research on Cancer, were used to calculate incidence rate ratios for 35 cancer sites, comparing men to women, adjusting for attained age, gross domestic product (GDP), and geographical region. Genital cancers and breast cancer were excluded. The consistency of relative risks was examined by GDP and geographical region and, in a subset of longstanding cancer registers, by calendar year. For each cancer site, the sex disparity was broadly classified as plausibly explained by established environmental risk factors, partly explained, or unexplained. Cancer incidence was statistically significantly higher in men than women at 32 of 35 sites, with disparities >2-fold for 15 sites and >4-fold for 5 sites. For nearly all sites, the sex disparity was consistent across GDP groups and geographical regions. However, the incidence rate ratios varied considerably by age at diagnosis. The sex disparity for 13 cancer sites was considered to be entirely unexplained by known risk factors; these sites showed strikingly little variation in the incidence rate ratios over decades. Thus, the basis of many of the largest sex disparities in cancer incidence seems mostly unknown, highlighting the need for intensified research into its origins.
A concern of reverse causation exists about the association between nasopharyngeal carcinoma (NPC) prognosis and body mass index (BMI) at diagnosis, while the prognostic impact of BMI measured years ...before diagnosis is unknown. Therefore, we investigated associations of prediagnosis and pretreatment BMI and body shape on NPC mortality. From a population‐based patient cohort in southern China between 2010 and 2013, we included 2526 incident NPC cases with prospective follow‐up through 2018. We assessed the associations of BMI and body shape at age 20 years, 10 years before diagnosis, and at diagnosis with NPC mortality, combining strategies of stratification and statistical adjustment to minimize reverse causation. We observed 25% lower all‐cause mortality (hazard ratio HR 0.75, 95% confidence interval CI: 0.64‐0.89) and 25% lower NPC‐specific mortality (HR 0.75, 95% CI: 0.61‐0.91) among overweight vs normal‐weight NPC cases at diagnosis. Lean body shapes 1 and 2 at diagnosis were associated with 68% and 23% higher all‐cause mortality, respectively, compared to normal body shape 3. No effect modification by cancer stage was detected for associations with all‐cause or NPC‐specific mortality. Associations with BMI and body shape 10 years before diagnosis were similar but attenuated, while body size and shape at age 20 were not associated with mortality. Being overweight at diagnosis decreased mortality, and thinner body shape increased mortality, compared to normal weight/body shape. These associations may be due to poorer nutrition and treatment intolerance, resulting in treatment discontinuation and worse survival outcomes.
What's new?
Body mass index (BMI) is suspected of influencing not only nasopharyngeal carcinoma (NPC) risk but also mortality after NPC diagnosis. Nonetheless, little is known about the impact of BMI at age 20 years and 10 years before NPC diagnosis and mortality. Here, in a population‐based patient cohort in southern China, the authors investigated associations between BMI and body shape at 20 years, 10 years before diagnosis and before treatment and NPC mortality. NPC mortality was decreased among patients who were overweight at diagnosis, whereas increased mortality was observed among thinner patients. Prediagnosis BMI and body shape had similar but weaker associations. Lean and underweight NPC patients may benefit from heightened clinical attention to undernutrition and poorer treatment tolerance.
To assess the independent effect of waist circumference on mortality across the entire body mass index (BMI) range and to estimate the loss in life expectancy related to a higher waist circumference.
...We pooled data from 11 prospective cohort studies with 650,386 white adults aged 20 to 83 years and enrolled from January 1, 1986, through December 31, 2000. We used proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs for the association of waist circumference with mortality.
During a median follow-up of 9 years (maximum, 21 years), 78,268 participants died. After accounting for age, study, BMI, smoking status, alcohol consumption, and physical activity, a strong positive linear association of waist circumference with all-cause mortality was observed for men (HR, 1.52 for waist circumferences of ≥110 vs <90 cm; 95% CI, 1.45-1.59; HR, 1.07 per 5-cm increment in waist circumference; 95% CI, 1.06-1.08) and women (HR, 1.80 for waist circumferences of ≥95 vs <70 cm; 95% CI, 1.70-1.89; HR, 1.09 per 5-cm increment in waist circumference; 95% CI, 1.08-1.09). The estimated decrease in life expectancy for highest vs lowest waist circumference was approximately 3 years for men and approximately 5 years for women. The HR per 5-cm increment in waist circumference was similar for both sexes at all BMI levels from 20 to 50 kg/m(2), but it was higher at younger ages, higher for longer follow-up, and lower among male current smokers. The associations were stronger for heart and respiratory disease mortality than for cancer.
In white adults, higher waist circumference was positively associated with higher mortality at all levels of BMI from 20 to 50 kg/m(2). Waist circumference should be assessed in combination with BMI, even for those in the normal BMI range, as part of risk assessment for obesity-related premature mortality.
Abstract Background Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other ...competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease. Objective To investigate the long-term natural history of untreated, early-stage PCa. Design, setting, and participants We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred. Outcome measurements and statistical analysis Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years. Results and limitations After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8–10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% 95% confidence interval, 48.4–89.3 to 25% 95% confidence interval, 22.0–72.5). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels. Conclusions Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis.
Time to abandon early detection cancer screening Adami, Hans‐Olov; Kalager, Mette; Valdimarsdottir, Unnur ...
European journal of clinical investigation,
March 2019, Letnik:
49, Številka:
3
Journal Article
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