Familial aggregation of childhood and adult cancer in the Utah genealogy

• Published in: International journal of cancer 2013-12, Vol.133 (12), p.2953-2960
• Main Authors: Neale, Rachel E., Stiller, Charles A., Bunch, Kathryn J., Milne, Elizabeth, Mineau, Geraldine P., Murphy, Michael F.G.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; age; Aged; Aged, 80 and over; Biological and medical sciences; Cancer; Case-Control Studies; Child; Child, Preschool; Children & youth; Epidemiology; familial risk; Families & family life; Family; Female; Genealogy; Genealogy and Heraldry; Genetics; Humans; Infant; Infant, Newborn; Male; Medical research; Medical sciences; Middle Aged; Neoplasms - epidemiology; Neoplasms - genetics; Risk factors; Tumors; Utah - epidemiology
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28300

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. What's new? The familial risk associated with childhood cancer is relatively understudied. Two reports in this issue of IJC report significantly increased cancer risks in relatives of children with cancer. Here, Neale and colleagues explored familial aggregation of cancer in a population‐based case‐control study in the US State Utah using genealogical record linkage. They report that mothers and siblings, but not fathers, of children with cancer are at increased risk of cancer in adulthood. The risk was higher in the relatives of younger children below five years of age. They specifically uncover a novel association between cancer in a child and risk of thyroid cancer in parents and show that the risk to develop any cancer is increased in relatives of children with leukemia. These findings point to yet to be discovered genetic factors that may mediate these associatio