Global variation in young adult central nervous system tumor incidence by region, age, and sex from 1988 to 2012

1

Introduction

In the United States, brain and central nervous system (CNS) tumors are among the top four cancers diagnosed in young adults aged 20–29 years of age with an average annual incidence rate of 10 cases/100,000 individuals [1] . Rates of brain tumors in Southern Europe are higher than those in the United States, but different histology groupings and time periods make comparisons across studies challenging [2] . While CNS tumor incidence is often reported to be lower in African nations, the lack of complete and comprehensive cancer registry coverage across the continent hinders true assessments of rates [3] . In a report from Japan, CNS tumors comprised less than 10% of tumors in young adults aged 29–39 years whereas germ cell tumors, breast and thyroid cancers dominated in incidence [4] . In contrast among young adults in the United States melanoma, thyroid tumors, and CNS tumors dominate in this age group [1] . In a previous Cancer Incidence in Five Continents (CI5) report of all adult CNS tumors covering 1993–2007, Brazil had the highest rates while Asian nations had the lowest suggesting that regional variation in incidence exists in all adults combined for regions studied [5] ; however, less is known about CNS tumor incidence in young adults aged 20–39 years specifically. A global study using the same histologic definitions, time periods and incidence measures is critical to understanding the burden of CNS tumors in young adults.

There are few established risk factors for brain tumor development aside from ionizing radiation [6] . However, there is a recognized male excess in brain and CNS tumors across the age spectrum from pediatrics [7] to adults [8] , suggesting that male sex itself is a risk factor for brain tumor development [9] . It is hypothesized that this male excess in incidence could be due to biologic sex differences rooted in the sex chromosome complement [10] along with sex differences in factors such as immune [11] and epigenetic [12] regulation. While circulating sex hormones clearly differ between males and females, it is hypothesized that they do not play a major role in brain tumor development as we observe a male excess in most tumor types in young children and adolescents [7] and into adulthood regardless of age-related hormone levels [9] . It is unknown whether this male excess persists across global regions. Should a male excess persist by region, this might suggest that the global variation in environmental risk factors or genetic ancestry do not largely contribute to the observed male excess thus pointing to a biologic role of sex in brain tumor development.

To address the lacking cohesion in the young adult CNS tumor incidence literature, we conducted a study using the CI5 data from 1988 to 2012 in individuals aged 20–39 years at diagnosis for six main histologic types. As young adulthood is a dynamic time in brain maturation [1314] and lifestyle factors such as reproduction are dominant in this age group, particularly for females, we stratified our analyzes by 10-year age groups to identify any potential windows of incidence importance. To better understand incidence trends in CNS tumors, we compared trends for the studied histologies across geographic regions captured in the CI5 by age, sex, and change in HDI.