• 2022-09
  • 2022-08
  • 2022-07
  • 2022-06
  • 2022-05
  • 2022-04
  • 2021-03
  • 2020-08
  • 2020-07
  • 2020-03
  • 2019-11
  • 2019-10
  • 2019-09
  • 2019-08
  • 2019-07
  • There are limitations to our study


    There are limitations to our study. First, routinely collected data has its limitation by nature – since CRC incidence increases with age, many people of younger age may not have lived up to the normal age range that the disease is typically developed yet. Since the cohort effect of younger generations are based on incidence in the younger age groups, there are more uncertainties towards the more recent birth cohorts as shown by the overlapping confidence intervals. A longer AUY922 (NVP-AUY922) of data collection would help clarify the effects on the more recent generations. Also, the observed age range and lengths of period varied across different populations under study. Even so, the time periods are long enough to generate reliable and comparable cohort estimates that generally went back to the turn of the 20th century. Second, the three components of age, period and cohort are linearly dependent on each other, making the full model with all three components non-identifiable without an additional reference constraint. Even with an additional constraint, only second-order changes in slope can be interpreted. To confirm our results, we also conducted APC modeling using the alternative method of partial least squares regressions [38], and found the same inflection points for all three effects (data not shown). Third, while we cannot rule out differences in reporting across years, hence a possible presence of the period effect, there is no reason to believe that these differences would occur in a systematic manner. Moreover, the present study used the most up-to-date data leading up to year 2007 for analysis. Since the lengths of follow-up period are longer for the older birth cohorts, there is stronger power and confidence to the findings of these older cohorts, thus enhancing robustness of our findings for international comparison. Last, this study treated CRC as one disease cluster, while in reality risk factors may differentially affect the various sub-sites (colon vs rectum, left colon vs right colon). Any future study would benefit from analysis by the different sub-sites. Nevertheless, the present study is a necessary first step to delineate the complex etiological risk factors of CRC with a global perspective.
    Declaration of conflicting interest
    Author statement
    Introduction Chronic myelomonocytic leukemia (CMML) is a rare hematopoietic malignancy characterized by peripheral monocytosis with overlapping features between myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). Depending on the predominant presentation, CMML can be sub-classified into a myelodysplastic (MD-CMML, WBC < 13 × 109/L) or myeloproliferative (MP-CMML, WBC ≥13 × 109/L) subtype [1]. Reactive monocytosis may be difficult to distinguish from CMML. Therefore, several follow-up investigations may be required for the correct diagnosis with integration of quantitative and qualitative features of peripheral blood and bone marrow. Multiparameter flow cytometry can contribute to find the correct diagnosis, but plays a minor role. Also conventional cytogenetics frequently reveal a normal karyotype at initial stages of the disease, whereas molecular genetics contributes increasingly to the identification of clonality. Difficulties may as well arise in the discrimination of CMML from other myeloid malignancies, such as advanced MDS, secondary acute myeloid leukemia (s-AML), or other MDS/MPN overlap syndromes. The incidence rate of CMML ranges from 0.3 to 0.7 per 100,000 person-years (py) with a median age at diagnosis above 70 years (yrs) and a male predominance [[2], [3], [4], [5], [6]]. Due to the demographic ageing of the general population, an increasing number of CMML patients is expected in the future with a growing impact on health system resources [7]. Population-based outcome data was recently reported from the Surveillance Epidemiology and End Results (SEER) database including 2238 CMML patients diagnosed between 2003 and 2013. Median survival declined with increasing age, ranging from 25 (age 20–29 yrs) to 11 months (age >80 yrs), and the main causes of death comprised progression into secondary acute myeloid leukemia (AML), bleeding and infection [3].