Molar pregnancy and childhood cancer: a population-based linkage study from Denmark

Abstract

We observed a relative risk of 1.40 (95% confidence interval; 0.86 -2.16) for cancers diagnosed under the age 20 in 6192 offspring of 3431 mothers with a molar pregnancy, indicating it is not a major determinant of childhood cancer. The few established causes of childhood cancer, including various chromosomal anomalies, account for only a small proportion of the total (Little, 1999). There is, however, evidence that certain types of childhood cancer originate in utero, although the underlying biological mechanisms are unclear (Hjalgrim et al, 2002). Maternal characteristics and pregnancy-related events have therefore been the focus of much research (Roman et al, 2005(Roman et al, , 2006. The population-based UK childhood cancer case -control study (UKCCS, 2000), which examined the obstetric records of mothers of 2962 childhood cancer cases aged 0 -14 years and 4864 matched controls found a statistically significant 2.5-fold increased childhood cancer risk among mothers with a previous molar pregnancy (Roman et al, 2005(Roman et al, , 2006, suggesting a common biological process. We therefore conducted a register-based cohort study in Denmark to examine cancer incidence in the offspring of women who had been diagnosed as having a molar pregnancy. MATERIALS AND METHODSWomen who had a molar pregnancy before 2005 were identified using the Danish National Hospital Register, which contains information for virtually all non-psychiatric hospital admissions in Denmark since 1977. Details of children born to these women were obtained from the National Central Population Register (CPR), which was established in 1968 with all citizens having unique personal identification numbers that permit linkage between registers. The follow-up for cancer incidence, determined by linking to the National Danish Cancer Registry which has been in operation since 1943 (Storm et al, 1997), was up to 31 December 2003, the most recent year with complete registration. Although there were no age restrictions for the linkage, we decided to include only cancers diagnosed before the age of 20 years in the analyses.In our analysis, the number of observed cases was compared with those expected. Expected numbers were determined by multiplying the number of person-years of cohort members by the incidence rates of primary cancer in the general population of Denmark (excluding non-melanoma skin cancer), in sex-specific 5-year age groups and 5-year calendar periods of observation. Standardised incidence ratios (SIRs) were calculated by dividing the observed and expected numbers, and exact 95% confidence limits of the SIRs obtained on the assumption of a Poisson's distribution of the observed cancers (Breslow and Day, 1987). Additional analyses involved restricting the age of follow-up to 14 years and to children born after their mother's molar pregnancy, the latter being primarily for comparison with previously published data (Roman et al, 2006). Data were also stratified by sex. RESULTSApproximately 1 million women gave birth between 1977 and 2005 from w...

Birth weight, sex and childhood cancer: A report from the United Kingdom Childhood Cancer Study

“…It is well documented that imprinting errors are responsible for certain adverse reproductive events, some of which convey increased risks of cancer and have differential sex effects. Indeed, we have previously reported an association between prior hydatididiform mole and cancer in subsequent offspring, suggesting perhaps that loss of imprinting may be responsible for both [38,39].…”