Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort.
BACKGROUND
Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown.


METHODS
We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat.


RESULTS
Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR = 11.9; 95% CI, 5.1-23.4; excess absolute risk = 7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR = 13.4; 95% CI, 1.6-48.6).


CONCLUSIONS
Our data are the first to indicate that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer.


CONCLUSIONS
Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies.
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
Anand
A
Pathak
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
Charleen D
CD
Adams
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
Jennifer T
JT
Loud
Westat, Inc., Rockville, Maryland.
Kathryn
K
Nichols
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
Douglas R
DR
Stewart
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. greenem@mail.nih.gov.
Mark H
MH
Greene
D000328:Adult; D005190:Family; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008396:Maryland / Q000453:epidemiology; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology* / Q000235:genetics; D010641:Phenotype; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D018426:SEER Program; D013736:Testicular Neoplasms / Q000453:epidemiology* / Q000235:genetics