Risks of cancer and families.

Journal of the National Cancer Institute, Vol. 97, No. 21, November 2, 2005 A cluster of cancers diagnosed in families raises concern about family risk and the need for counseling. Because family members share similar genes or may have experienced common environmental challenges, it would not be surprising to fi nd clusters of cancers in families. The investigation by Bermejo and Hemminki ( 1 ) raises some provocative questions regarding a family member being diagnosed with cancer and other family members later being diagnosed with the same cancer. Bermejo and Hemminki used the Swedish Family Cancer Database to explore the pattern of familial risk after diagnosis of the fi rst cancer in a family. The main theme in the analysis was to determine if the fi rst cancer diagnosed in a family would motivate other family members to seek examinations for cancer. If true, this would most likely lead to increased diagnoses of other family members in the period shortly after the diagnosis of the fi rst cancer and would artifi cially infl ate the cancer risk. The authors refer to this bias as “ surveillance bias. ” The cancers that are investigated are breast, prostate, colorectal, cervix, lung, and invasive melanoma. The authors present data in which a parent is a proband and similar data in which a sibling is a proband. The methodology of the study was that the fi rst person diagnosed with cancer in a family was designated as the proband. If the proband is a parent, the offspring of the proband were followed from the proband’s year of diagnosis until a diagnosis of cancer (invasive or in situ), death, or until some other noncancer endpoint was reached in the offspring. If the proband is a sibling, other siblings were followed for cancer diagnosis. Relative risks were calculated to compare the incidence among relatives of probands with the incidence of cancer in the general population. One would expect that if surveillance bias is present, a cancer diagnosis in a family would be highest in the year in which the proband’s cancer was diagnosed and would taper off with more follow-up time. If the mean preclinical sojourn time for asymptomatic cancers is short, however, this method of analysis would be unlikely to result in increased relative risk, whereas if the mean preclinical sojourn time is relatively long, the method could show the existence of surveillance bias. The methodology requires further discussion. It is necessary to distinguish between parent and sibling probands, as the authors have done. If a comparison of parent – offspring pairs is made in which the parent is the proband, detecting cancer in an offspring depends on the number of offspring in the family. The more offspring, the higher the likelihood that there will be a family member who will have another similar cancer. Therefore, the cancer risk depends on family size. Thus, the observed risk of the offspring will not be appropriate as an estimate of individual cancer risk unless there is an adjustment for family size. However, because the numerator and denominator in the relative risk ratio were calculated from the same database, it would be expected that the distribution of family size would similarly affect both the numerator and denominator. The mixture of EDITORIALS