Do parents and grandparents of patients with achondroplasia have a higher cancer risk?
Several studies, performed according to hypotheses based on teratogenesis and carcinogenesis have tried to answer the question: Do parents of children with congenital anomalies have a higher cancer risk? If the general answer is no, however, a higher risk for cancer was reported in the parents of children with cleft lip/palate (Zhu et al. [2002: Br J Cancer 87:524-528]). In achondroplasia, the neo-mutations are from paternal origin raising the hypothesis of the existence of a "mutator" gene acting in male meiosis and in somatic, mitotic cells in both sexes which may favor also the occurrence of cancer. In order to test this hypothesis, a questionnaire was sent to people with non-familial achondroplasia, asking for cancer, lymphoma, and leukemia in their parents and grandparents. In the hypothesis tested, the maternal lineage was the control. One hundred forty eight answers were obtained from 76 males and 72 females with achondroplasia. Out of them 68 had parents and/or grandparents with cancer. Among the grandparents of people with achondroplasia there were 36 cancers including two lymphomas in the paternal grandparents, 20 cancers including two chronic myeloid leukemia (CML) in the paternal grandmothers, 22 cancers including two CML in the maternal grandfathers, and two cancers in the maternal grandmothers. Paternal grandfathers and grandmothers had significantly more cancers (56) than maternal grandfathers and grandmothers (24) (chi(2)-test = 14.80, P < 0.001). In conclusion, paternal grandfathers and grandmothers of people with achondroplasia had significantly more cancers than maternal grandfathers and grandmothers. This result raises hypotheses in relationship with the paternal origin of neo-mutations in achondroplasia.
Stoll
C
C
Laboratoire de Genetique Medicale, Faculte de Medecine, 67085 Strasbourg Cedex, France. Claude.Stoll@medecine.u-strasbg.fr
Feingold
J
J
D000130:Achondroplasia / Q000235:genetics*; D016009:Chi-Square Distribution; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors; D011795:Surveys and Questionnaires