Mutagenesis, Vol. 17, No. 5, 445-446,
September 2002
© 2002 UK Environmental Mutagen Society/Oxford University Press
LETTER TO THE EDITOR |
Concerning the CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis
1 Department of Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Road, NW Atlanta, GA 30329-4251, US, 2 Department of Preventive Medicine, University of Southern California Keck School of Medicine, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, MS # 44, Los Angeles, CA 90033-0800, US
Ye and Parry (2002) recently presented a meta-analysis of the CYP17 MspA1 polymorphism and breast cancer. While it is appealing to come up with a summary effect across studies, a meta-analysis is not the best approach to resolve the CYP17–breast cancer association. A meta-analysis for this set of data is of questionable validity, as the studies that have been done employ different designs and include a mixture of ages and ethnicities.
Regarding the published meta-analysis, we noticed several errors in reporting the number of advanced cases and controls in Table II. In some instances, this led to an incorrect specification of control groups when estimating the effect of the CYP17 A2 allele for advanced breast cancer. For some of the studies, Ye and Parry used odd ratios (ORs) that were computed by comparing advanced to localized cases, rather than advanced cases to unaffected controls. The two methods address different questions regarding the role of CYP17 in the etiology of breast cancer.
When summarizing data from previous articles, Ye and Parry did not include data from our recent study (Feigelson et al., 2001
) in their calculation of a summary estimate for advanced breast cancer (Table II in Ye and Parry, 2002). Our nested case control study included 615 stage 1 cases, 235 cases of stage 2 or greater (`advanced') and 1508 controls (in situ cases and those of unknown stage were excluded). These 235 cases represent the largest number of advanced cases from a single study in the published literature to date. Among advanced cases we found that compared to A1/A1 women, those with the A1/A2 genotype had a RR = 1.29 (95% CI 0.93–1.75) and those with the A2/A2 genotype had a RR = 1.45 (95% CI 0.96–2.20) with a borderline significant test for trend (p = 0.05).
In Table I, we have recalculated summary ORs for the effect of the CYP17 MspAI polymorphism and advanced breast cancer. We have included the same studies as Ye and Parry (Helzlsouer et al., 1998; Weston et al., 1998; Bergman-Jungestrom et al., 1999; Haiman et al., 1999; Kristensen et al., 1999; Mitrunen et al., 2000), with the addition of our data for advanced breast cancer. All of the ORs in Table I compare advanced cases with unaffected controls. We used adjusted ORs when provided by the original authors and calculated crude ORs when allele frequencies by advanced case and control status were provided. We did not calculate crude ORs for one study that employed a matched design (Helzlsouer et al., 1998), as doing so would introduce confounding.
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Our meta-analytic results suggest that the A2 allele may confer a small increased risk for breast cancer, although the confidence intervals remain wide (summary OR = 1.39, 95% CI 0.89–2.16 for A2/A2 compared with A1/A1). This estimate is very different from that of Ye and Parry (OR = 0.96, 95% CI 0.77–1.20). Our summary estimate for the A2/A2 allele is based on only four studies, with a total of 519 cases of advanced breast cancer, thus drawing conclusions from this limited amount of data must be done cautiously and considered in context with other available data.
Given the many pitfalls and limitations of meta-analysis (Greenland, 1994), exceptional rigor should be applied when attempting to summarize the data using the meta-analytic approach. As can be seen from comparing our summary estimates with those of Ye and Parry, choices in study inclusion can result in very different interpretations of the data.
Notes
To whom correspondence should be addressed. Tel: +1 404 929 6815; Fax: +1 404 327 6450; Email: Heather.Feigelson{at}cancer.org
References
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Bergman-Jungestrom,M., Gentile,M., Lundin,A.-C., Group,S.-E.B.C. and Wingren,S. (1999) Association between CYP17 gene polymorphism and risk of breast cancer in young women. Int. J. Cancer, 84, 350–353.[Web of Science][Medline]
Feigelson,H., McKean-Cowdin,R., Coetzee,G., Stram,D., Kolonel,L. and Henderson,B. (2001) Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates. Cancer Res., 61, 785–789.
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Mitrunen,K., Jourenkova,N., Kataja,V., Eskelinen,M., Kosma,V.M., Benhamou,S., Vainio,H., Uusitupa,M. and Hirvonen,A. (2000) Steroid metabolism gene CYP17 polymorphism and the development of breast cancer. Cancer Epidemiol. Biomarkers Prev., 9, 1343–1348.
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Ye,Z. and Parry,J.M. (2002) The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis. Mutagenesis, 17, 119–126.
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