Heterogeneity of risk for melanoma and pancreatic and digestive malignancies: a melanoma case-control study.
BACKGROUND
Data addressing the interfamilial heterogeneity of melanoma are limited. In the current study, the authors assessed melanoma risk according to family history of melanoma and other melanoma-associated malignancies and evaluated the familial heterogeneity of melanomas, pancreatic malignancies, and gastrointestinal malignancies.


METHODS
The authors obtained patient histories of malignancy in first-degree relatives as part of a clinic-based case-control study. The case group included 737 newly diagnosed patients with invasive melanoma, and the control group included 1021 outpatients from clinics at the same medical centers. To assess heterogeneity of risk among families affected by melanoma, a nonparametric method was used to detect extrabinomial variation. In addition, selected patients with melanoma (n=133) were tested for germline mutations in CDKN2A.


RESULTS
The adjusted odds ratio associated with a family history of melanoma was 1.7 (95% confidence interval, 1.1-2.7). Family histories of pancreatic, gastrointestinal, brain, breast, or lymphoproliferative disease did not increase the risk of melanoma significantly. Among case families, significant evidence of familial heterogeneity was found for melanomas, but not for pancreatic or gastrointestinal malignancies. Two mutations in CDKN2A previously associated with melanoma risk were identified among the 133 patients tested in the case group; mutation detection did not differ between families with low and high heterogeneity scores.


CONCLUSIONS
Familial heterogeneity testing in the study population did not improve the selection of high-risk families for genetic study. Even in a large case-control study, few families that had multiple members with melanoma were identified, and family members with pancreatic malignancies were rare.
Rutter
Joni L
JL
Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-7236, USA.
Bromley
Christina M
CM
Goldstein
Alisa M
AM
Elder
David E
DE
Holly
Elizabeth A
EA
Guerry
Dupont
D
Hartge
Patricia
P
Struewing
Jeffery P
JP
Hogg
David
D
Halpern
Allan
A
Sagebiel
Richard W
RW
Tucker
Margaret A
MA
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005192:Family Health; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D019942:Genes, p16; D018740:Genetic Heterogeneity; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D012307:Risk Factors