© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 4, 324-325,
February 21, 2001
© 2001 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: High Frequency of Multiple Melanomas and Breast and Pancreas Carcinomas in CDKN2A Mutation-Positive Melanoma Families
Affiliations of authors: H. Olsson (Department of Oncology and South Swedish Regional Tumour Registry), H. Andersson, A. Bladström, T. Möller (South Swedish Regional Tumour Registry), Å. Borg (Department of Oncology), C. Ingvar, J. Westerdahl (Department of Surgery), University Hospital, Lund, Sweden.
Correspondence to: Håkan Olsson, M.D, Ph.D., Department of Oncology, University Hospital, Lund 22185, Sweden (e-mail: hakan.olsson{at}onk.lu.se).
We fully agree with Drs. Plna and Hemminki that genes from both the maternal and paternal sides might contribute to the overall incidence of cancer in offspring, even in the setting of hereditary cancer syndromes. For example, such genes might increase disease penetrance or modify tumor phenotype. This phenomenon may at least partly explain why some families with CDKN2A mutations also develop breast or pancreatic cancer. Unpublished data from our group (Olsson H, Johannsson O, Loman N) suggest that, in families with hereditary cancer syndromes with a high disease penetrance, cancer incidence is also increased above expected levels in family members who do not carry the cancer-predisposing mutation.
In addition, we have evidence of a geographic heterogeneity in Sweden of the familial incidence of malignant melanoma and breast cancer. We have previously used the same database as Hemminki and co-workers for Sweden as a whole in publications on colorectal cancer and breast cancer (1,2); here, we consider the geographic distribution of familial breast cancer and malignant melanoma risk in relation to the site of residence of the mother at time of diagnosis (Table 1
). The highest risk for melanoma when the mother had melanoma diagnosed before age 50 years is seen in the southeastern, Stockholm–Gotland, and southern regions of Sweden, corresponding to the geographic distribution of families carrying the known CDKN2A founder mutation that is thought to have originated in the southeastern region of Sweden about 107 generations ago (3,4).
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If we look at breast cancer in a similar way, the northern region of Sweden has a statistically significantly lower incidence of breast cancer in the female offspring than the rest of the country (P = .04). (Table 1
). This difference is more pronounced if the mother is young. The offspring of young mothers with breast cancer do not show a statistically significantly increased melanoma incidence; however, the offspring of older women with breast cancer in the western, Stockholm-Gotland, and southern regions of Sweden (i.e., regions that do not fully correspond with the origin of the CDKN2A founder mutation) have a statistically significantly higher risk of malignant melanoma. The data thus suggest another breast cancer–melanoma relationship in older patients with breast cancer than the one associated with the CDKN2 founder mutation. The overall lower familial incidence of breast cancer in northern Sweden could perhaps be attributable to the influence of genes from people of Finnish and Laplandic origins in this part of Sweden. These results thus suggest that targeting searches for cancer-predisposing genes to families of a specific geographic origin in Sweden might be especially worthwhile.
REFERENCES
1 Planck M, Andersson H, Bladstrom A, Moller T, Wenngren E, Olsson H. Increased cancer risk in offspring of patients with colorectal carcinoma: a Swedish register-based cohort study. Cancer 2000;89:741–9.[CrossRef][Web of Science][Medline]cancerlit;20408799
2
Anderson H, Bladstrom A, Olsson H, Moller TR. Familial breast and ovarian cancer: a Swedish population-based register study. Am J Epidemiol 2000;152:1154–63.
3
Borg A, Sandberg T, Nilsson K, Johanssson O, Klinker M, Masback A, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst 2000;92:1260–6.
4 Hashemi J, Bendahl PO, Sandberg T, Platz A, Linder S, Stierner U, et al. Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in Swedish melanoma families. Genes Chromosome Cancer. In press 2001.
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