Having Sons Reduces the Risk of Prostate Cancer
Having Sons Reduces the Risk of Prostate Cancer
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC. Dr. Ershler reports no financial relationship to this field of study.
Synopsis: In a family-based research cohort, men were followed for up to 40 years after the birth of their children, and those with only daughters had a 40% higher risk of prostate cancer compared with men with at least one son. The findings support the hypothesis that Y chromosome loci are involved in the pathogenesis of prostate cancer.
Source: Harlap S, Platiel O, Friedlander Y, Calderon-Margalit R, Deutsch L, Kleinhaus KR, Manor O, Neuget AI, Opler M, Perrin MC, Terry MB, Tiram E, Yanetz R. Prostate cancer in fathers with fewer male offspring: The Jerusalem Perinatal Study Cohort. J Natl Cancer Inst. 2007;99:77-81.
There have been recent studies suggesting the involvement of loci on the Y chromosome in the pathogenesis of prostate cancer. Because mutations or variants in sex chromosomes might influence the gender of offspring, the current study was designed to determine whether the risk of prostate cancer is associated with offspring gender. For example, mutations on the Y chromosome associated with prostate cancer (as postulated) may also reduce the likelihood of male offspring.
To address this question, investigators surveyed vital status and cancer incidence in fathers from the Jerusalem Perinatal Study, a family-based research cohort.1 Over a 13-year period (1964-1976), all births to residents in western Jerusalem (n = 92,408) were recorded and demographic features of parents and grandparents abstracted. By linking with the Israel Cancer Registry it was discovered that a total of 712 of the fathers had developed prostate cancer. Compared with men who had at least one son, men with only daughters had an increased risk of prostate cancer (adjusted relative risk [RR] = 1.40, 95% confidence interval [CI] = 1.20 to 1.64, P < 0.0001). In men with one, two, or three or more offspring, the relative risks associated with absence of sons were 1.25 (95% CI = 1.00 to 1.56), 1.41 (95% CI = 1.04 to 1.91), and 1.6 (CI I.05 to 2.43), respectively. Men with no daughters showed no statistically significant altered risk, compared with men who had offspring of both sexes. The relative risk of prostate cancer decreased as the numbers of sons increased (Ptrend < 0.0001) but did not change with the number of daughters.
Commentary
These findings support the hypothesis that Y chromosome loci are involved in prostate cancer and provide an excellent example of how careful epidemiological investigation can provide basic clues to the pathogenesis of disease. Of course, other explanations may be forwarded. One that came to mind was that perhaps men with daughters are more likely to be screened and thus diagnosed. However, if such were the case, earlier diagnosis would be expected in those with daughters and better survival observed. This was not the case. Furthermore, the lack of sons appeared to have biological significance, as it becomes increasingly important as family size increases.
Although the postulated genetic loci on the Y chromosome remain to be identified, further research capitalizing on this observation may be productive. Prior work had suggested involvement of sex chromosomes, both X.2, 3 and Y. The incidence of prostate cancer is increased in some4, 5 families carrying mutations in BRCA1 or BRCA2. In such families, regardless of whether they include men with prostate cancer, male carriers have a lower percentage of male offspring than the general population.6, 7 This was also found in two case-control studies of the offspring of BRCA-associated prostate cancer patients.8, 9 Thus, the Jerusalem Perinatal Study provides additional evidence that function of the Y chromosome is altered in some ways in at least some with prostate cancer. Further investigation in the laboratory, but using clinical samples, may ultimately reveal the specifics of this Y chromosome defect.
References
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2. Monroe KR, et al. Nat Med. 1995;1(8):827-829.
3. Tung KH, et al. Am J Epidemiol. 2004;159(8):750-758.
4. Kirchhoff T, et al. Clin Cancer Res. 2004;10(9):2918-2921.
5. Lorenzo Bermejo J, et al. Ann Oncol. 2004;15(12):1834-1841.
6. Chenevix-Trench G, et al. Fam Cancer. 2005;4(2):73-75.
7. Struewing JP, et al. Eur J Hum Genet. 2004;12(8):663-667.
8. Hsieh CC, et al. Int J Cancer. 1999;80(5):699-703.
9. Negri E, et al. Int J Cancer. 2005;114(4):648-652.
In a family-based research cohort, men were followed for up to 40 years after the birth of their children, and those with only daughters had a 40% higher risk of prostate cancer compared with men with at least one son.Subscribe Now for Access
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