Date Published: January 16, 2007
Publisher: Public Library of Science
Author(s): Pagona Lagiou, Dimitrios Trichopoulos
Partial Text: The study of family of origin (parental family), as contrasted to family of procreation, originally received attention from epidemiology in the context of childhood infectious diseases. Two aspects of parental family have been intensely investigated: sibship size and birth order [1,2]. Larger sibship size increases the likelihood of introduction and spread of infectious agents within the family and tends to be inversely associated with children’s average age at infection. Birth order, in the absence of vaccination, has a more specific effect on average age at infection, since first-born children are usually infected when first exposed to the child care or school environment, whereas later-born children tend to be infected earlier, even in utero, by their older siblings.
Larger sibship size and higher birth order have long been known to be associated with higher prevalence of chronic infections by the hepatitis B virus . More recently, similar associations have been reported for infection with Helicobacter pylori . Clearly, since these microorganisms are etiologically related to hepatocellular carcinoma and gastric adenocarcinoma, respectively, sibship size and birth order should be—and have been reported to be [5,6]—risk factors for these malignancies.
In a cohort of 9,935 Japanese-American men, who had provided blood samples at entry in the study and were followed for 28 years, 261 cases of non-cardia gastric cancer were identified. In a nested case-control design, each case patient was paired with one control, matched for age at examination and date of serum collection. Of the 261 patients with non-cardia gastricEarlier age at establishment of H. pylori carrier state increases the risk of gastric cancer decades later. cancer, 239 (92%) were carriers of H. pylori on the basis of antibody status and 189 (72%) carried cagA+ strains, which are considered more virulent. The corresponding numbers and proportions among the 261 matched controls were 205 (79%) and 155 (59%). In line with the study objective, further analyses were restricted to patients who were serologically positive for H. pylori in general or cagA+ in particular cases and controls.
Blaser and colleagues  have used an important cohort to evaluate evolving concepts on the natural history of H. pylori infection and have reached conclusions that are of both theoretical and practical importance. A limitation of their study is the relatively small number of cases with gastric adenocarcinoma but, clearly, not much could be done about this. Another limitation is that mutual control of sibship size and birth order was not attempted. These two variables are strongly positively correlated (one cannot have a high birth order unless one belongs in a large sibship) and association of gastric cancer with just one of them would be reflected in an association with the other as well. In this instance, however, since increases in both of these variables tend to reduce age at infection, the reported associations point to a biologically sound and valuable conclusion.
A broader lesson from this study is that age at infection or establishment of chronic carrier state is a variable of considerable importance in assessing the carcinogenic potential of infectious agents. These consequences are unlikely to be uniform across the various cancer types—we already have evidence that late infection with unspecified agent(s) increases the risk of childhood leukemia [11,12]. Identifying the agents’ molecular characteristics or the hosts’ immunological aspects in early or late infection is a field that merits further attention in the study of cancer etiology.