Familial aggregation of childhood and adult cancer in the Utah genealogy

Abstract

A small proportion of childhood cancer is attributable to known hereditary syndromes, but whether there is any familial component to the remainder remains uncertain. We explored familial aggregation of cancer in a population-based case-control study using genealogical record linkage and designed to overcome limitations of previous studies. Subjects were selected from the Utah Population Database. We compared risk of cancer in adult first-degree relatives of children who were diagnosed with cancer with the risk in relatives of children who had not had a cancer diagnosed. We identified 1,894 childhood cancer cases and 3,788 controls; 7,467 relatives of cases and 14,498 relatives of controls were included in the analysis. Relatives of children with cancer had a higher risk of cancer in adulthood than relatives of children without cancer [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.11-1.56]; this was restricted to mothers and siblings and was not evident in fathers. Familial aggregation appeared stronger among relatives of cases diagnosed before 5 years of age (OR 1.48, 95% CI 1.13-1.95) than among relatives of cases who were older when diagnosed (OR 1.22, 95% CI 0.98-1.51). These findings provide evidence of a generalized excess of cancer in the mothers and siblings of children with cancer. The tendency for risk to be higher in the relatives of children who were younger at cancer diagnosis should be investigated in other large data sets. The excesses of thyroid cancer in parents of children with cancer and of any cancer in relatives of children with leukemia merit further investigation.The causes of childhood cancer are largely unknown. A small proportion of cases are attributable to known hereditary cancer syndromes, but whether there is any familial component to the remainder remains uncertain. Understanding familial risks may help to further elucidate etiology and/or identify the need to screen family members.Little 1 reviewed much of the already extensive literature published to 1997 on aggregation of cancer among firstdegree relatives of children with cancer. Many of these studies involved a relatively small number of cases, and Little concluded that there was no strong evidence of familial risks in parents or siblings for most of the common types of childhood cancer. Since then, several large studies of cancer risk in first-degree relatives of children with cancers of all types have emerged from the Nordic countries, 2 the United Kingdom, 3 the United States 4 and Italy. 5,6 Analyses of risk for many types of childhood cancer have also been published from the Swedish Family Cancer Database. 7-9 There has been broad agreement that overall the risk of childhood cancer in the siblings of children with cancer is moderately increased. 2,10,11 In a population-based study in the Nordic countries, there was a small increase in the risk of cancer in siblings of all ages combined, but this was entirely accounted for by known familial cancer syndromes. 2 Conversely, a North American study of the siblings of 5-y...

Cancer Risks for Relatives of Children with Cancer

“…These findings were seen in both first- and second-degree relatives. Although some of our findings did not reach statistical significance, they are largely consistent with previously published unselected childhood cancer cohorts [5–7, 12] and add to a growing body of evidence that unidentified genetic risk exists in some families. In addition to the small size of the study, other limitations include the use of family history in isolation and the absence of some parental input to family history of cancer.…”

“…The apparent association of childhood cancer with adult cancers in female relatives is fascinating and supports a recently published population-based study from Utah, USA [5], where a higher risk of adult cancer was restricted to mothers and siblings (SIR 1.31; 95% CI 1.11–1.56) but was not observed in fathers [5]. It is interesting to note that the effect was greatest for children younger than 5 years at diagnosis (SIR 1.48; 95% CI 1.13–1.95), suggesting a strong ante- or perinatal effect.…”

“…Beyond this, it is not clear if cancer in childhood increases the risk of cancer in relatives. A number of recent studies have described an association between childhood cancer and cancer in first-degree relatives [5–7], particularly siblings [5, 7] and mothers [5]. In this study, we describe the distribution of cancers in Australian children and estimate the risks of cancer in their relatives.…”

Implementing family health history risk stratification in primary care: Impact of guideline criteria on populations and resource demand

“…Genetic counseling is an already limited commodity and few PCPs have an established relationship with a genetic counselor or medical geneticist. While increased training in these fields will help, broader adoption of alternative counseling modalities such as telegenetics and phone counseling can expand access and help to accommodate increases in demand [Hemminki et al, 2008;Neale et al, 2013]. For colon cancer screening, PCPs and gastroenterologists may end up sharing the additional workload, depending upon screening modality (in some recommendations colonoscopy is re-quired, but in others any screening modality is acceptable).…”

“…These data highlight the importance of understanding FHH risk factors, their prevalence, and their relationship to outcomes in order to inform guideline development. However, in contrast to sensitivity and specificity for which data exists, surprisingly little is known about prevalence in the general population and what is published references selected populations, typically probands affected by a disease of interest [Hemminki et al, 2008;Grimes et al, 2012;Neale et al, 2013]. In addition, guideline development teams rarely, if ever, consider the downstream consequences of implementation.…”