© The Author 2006. Published by Oxford University Press.
CORRESPONDENCE |
RESPONSE: Re: Association Between Endothelin Receptor B Nonsynonymous Variants and Melanoma Risk
For the Investigators of Melan-Cohort
Affiliation of Authors: Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, AP-HP, Faculté de Médecine, Paris, France
Correspondence to: Nadem Soufir, MD, PhD, Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, AP-HP, Faculté de Médecine, Paris VII, IFR02, France (e-mail: nadem.soufir{at}bch.ap-hop-paris.fr).
Thirumaran et al. raise concerns about the true association of the S305N EDNRB mutation with melanoma risk that we previously reported in a case–control study. Even though the study by Thirumaran et al. has a larger number of patients and control subjects than ours, we want to point out several differences with our study. First, we observed that, in contrast to our work, case patients and control subjects were not matched by sex; the number of men in the control group was more than twice that of women (M/F = 2.15), although the number of male and female patients was similar (M/F = 1.2) (two-sided P<.001). Second, case patients and control subjects were not matched by age; the median age of control subjects was less than that of case patients (41 years versus 57 years). Although the odds ratios were adjusted for age and sex, these data may have lowered the power of the statistical analysis by diminishing the number of the subjects that were compared after adjustment.
In addition, in the group of patients we studied, many had familial melanoma (29 of 137, 21%), and we observed that the S305N mutation was statistically more frequent in familial melanoma than in sporadic melanoma (5 of 29 versus 7 of 118, two-sided P = .046). If the study of Thirumaran et al. comprised fewer patients with familial melanomas, conclusions about the differences observed in the S305N allele frequency need to be taken with caution.
Finally, in our study, the association between EDNRB gene polymorphisms and risk of melanoma was stronger when we included all nonsynonymous EDNRB variants in our analysis than when we analyzed the S305N variant alone. This has been previously observed for MC1R, a well-established low-penetrance melanoma predisposing gene. When only few MC1R variants were examined, no association with melanoma could be detected (1), whereas the association of MC1R with melanoma was clearly shown when all MC1R variants were taken into account (2–4). In line with this, Thirumaran et al. do not rule out that other EDNRB variants could be associated with melanoma, as they did not sequence the entire EDNRB coding region. As with other polygenic diseases, further replication studies and meta-analyses are needed to resolve this question.
REFERENCES
(1) Ichii-Jones F, Lear JT, Heagerty AH, Smith AG, Hutchinson PE, Osborne J, et al. Susceptibility to melanoma: influence of skin type and polymorphism in the melanocyte stimulating hormone receptor gene. J Investig Dermatol 1998;11:218–21.
(2) Kennedy C, ter Huurne J, Berkhout M, Gruis N, Bastiaens M, Bergman W, et al. Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Investig Dermatol 2001;117:294–300.[CrossRef][Web of Science][Medline]
(3) Matichard E, Verpillat P, Meziani R, Gerard B, Descamps V, Legroux E, et al. Melanocortin 1 receptor (MC1R) gene variants may increase the risk of melanoma in France independently of clinical risk factors and UV exposure. J Med Genet 2004;41:e13.
(4) Landi MT, Kanetsky PA, Tsang S, Gold B, Munroe D, Rebbeck T, et al. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J Natl Cancer Inst 2005;97:998–1007.
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J Natl Cancer Inst 2006 98: 1252-1253.
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