Genetic contributions to the association between adult height and testicular germ cell tumors

Abstract : Testicular germ cell tumors (TGCT) have an unusual incidence pattern relative to the majority of other neoplasms. TGCT incidence peaks at approx. 30 years and rapidly declines thereafter. Research into TGCT aetiology has, thus, focused upon pre-natal, perinatal and adolescent stages of development. The most consistent factors associated with risk of TGCT are previous history of TGCT, family history of TGCT and cryptorchidism, whereas meta-analytic synthesis of the available evidence suggests that inguinal hernia, twinning, maternal bleeding, low birth-order and small sibship size may also be risk factors for TGCT. Previously, we, and others, found that increased adult height is also associated with increased risk of TGCT, with the majority of such reports indicating a monotonic relationship. The cause of this association remains largely uninvestigated but may be an important aetiological factor given that average male height and incidence of testicular cancer have both been increasing over several generations with strong cohort effects. Adult height is considered to be determined by both environmental and genetic effects. The quality of early childhood nutrition is thought to be integral to adult height attained, with environmental factors in total being responsible for 20% of the variability observed. In many populations of Western Europe and North America, the heritability of adult height is estimated to be 80%. Recent agnostic approaches in the form of genome-wide association studies have found several genetic loci associated with adult height which, in combination, have been estimated to explain approx. 3-4% of the population variability of this polygenic trait. We examined whether single-nucleotide polymorphisms (SNPs), previously associated with adult height, could explain the association between adult height and risk of TGCT.