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A Systematic Review Of Genetic Polymorphisms and Breast Cancer Risk¹

Cancer Research Campaign Human Cancer Genetics Group, University Department of Oncology [A. M. D., C. S. H., P. D. P. P., B. A. J. P.], and Cancer Research Campaign Genetic Epidemiology Group, University Department of Community Medicine [M. D. T., D. F. E.], Strangeways Research Laboratories, Worts Causeway, Cambridge CB1 8RN, United Kingdom

	Abstract

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
Studies investigating the relationship between common genetic variants and cancer risk are being reported with rapidly increasing frequency. We have identified 46 published case-control studies that have examined the effect of common alleles of 18 different genes on breast cancer risk. Of these, 12 report statistically significant associations, none of which were reported by more than one study. However, many of the studies were small: 10 of the 46 had 80% power or greater to detect a rare allele homozygote relative risk <2.5. We therefore combined the results of individual studies to obtain more precise estimates of risk. Statistically significant differences in genotype frequencies were found in three case-control comparisons of unselected cases. These were for CYP19 (TTTA)_n polymorphism [(TTTA)₁₀ carrier odds ratio (OR) = 2.33; P = 0.002], the GSTP1 Ile105Val polymorphism (Val carrier OR = 1.60; P = 0.02), and the TP53 Arg72Pro polymorphism (Pro carrier OR = 1.27; P = 0.03). In addition, the GSTM1 gene deletion was found to be significantly associated with postmenopausal breast cancer (null homozygote OR = 1.33; P = 0.04). There was also some evidence that homozygotes for the PR PROGINS allele are protected against breast cancer, although this result was of borderline statistical significance. For polymorphisms in BRCA1, COMT, CYP17, CYP1A1, NAT1, and NAT2, the best estimate of risk either from the individual studies or the meta-analyses was sufficiently precise to exclude a relative risk of 1.5 or greater. For the polymorphisms in EDH17B2, ER, CYP2D6, CYP2E1, GSTT1, HSP70, and TNF, the risk estimates, although nonsignificant, were insufficiently precise to exclude a moderate risk (>1.5). Precise estimation of the risks associated with these and other as yet untested genes, as well as investigation of more complex risks arising from gene-gene and gene-environment interactions, will require much larger studies.

	Introduction

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
Breast cancer is a common disease in Western societies, with a lifetime prevalence of 1 in 12 in the United Kingdom (1) and 1 in 8 in the USA (2) . Although 10–15% of breast cancer cases have some family history of the disease, only 5% can be explained by rare, highly penetrant mutations in genes such as BRCA1 and BRCA2 (3) First-degree relatives of breast cancer patients have a 2-fold increase in risk over the general population (4) , most of which cannot be accounted for by BRCA1/2 (5) . Although some of the familial risk may be due to shared environment, there may be other common, low-penetrance genetic variants which alter predisposition to breast cancer.

A frequently used experimental design for identifying common low-penetrance alleles is the association study (6) . In this design, polymorphic genotype frequencies are compared between groups with different phenotypes. The aim is to study polymorphisms that may either be causally related to disease risk or are in strong linkage disequilibrium with disease-causing variants. Phenotypes investigated can be either continuously variable, such as serum lipid levels, or discrete, such as disease cases versus matched controls, in which instance the study design is a classic case-control study. The simplest polymorphisms to use are biallelic, which most commonly arise from a SNP,⁴ and give rise to three different genotype classes: the common allele homozygote, the heterozygote, and the rare allele homozygote. Multiallelic, repeat length polymorphisms (microsatellites), such as the (TTTA)_n polymorphism in CYP19, can also be used, but these usually give rise to many genotypes. Genotypes often are grouped to simplify analysis, but this is valid only if a rational grouping strategy can be applied. Furthermore, the higher mutation rate in microsatellites is likely to lead to weaker associations unless the polymorphism itself is functional (e.g., the androgen receptor polyglutamine tract and prostate cancer risk). Genetic association studies using populations are more powerful than linkage studies within pedigrees for identifying low-penetrance alleles, which by definition may not be expressed in multiple members of a single family (7) . However, at present, association studies can be carried out only on candidate genes.

There are a variety of ways of presenting gene polymorphism data in relation to breast cancer risk, depending on the nature of the polymorphism. In the case of simple biallelic polymorphisms, allele frequencies in cases and controls can be compared using the ² test to ascertain statistical significance. However, this method does not produce an easily interpretable measure of the magnitude of breast cancer risk and also lacks statistical power compared with some alternatives. A more appropriate method is to compare genotype frequencies of the three possible genotypes among cases and controls. The relative risk of breast cancer for each genotype is then estimated by the OR. The baseline group is usually the common allele homozygote, which by definition has an OR (and relative risk) of 1. Depending on the allele frequencies, the number of rare allele homozygotes may be very small, particularly in small studies, and the associated OR will have a wide confidence interval. Under these circumstances, it is common to combine the heterozygotes and rare-allele homozygotes and calculate the rare allele carrier OR. However, this risk estimate is valid only if the genetic model is dominant, an assumption that should not be made without appropriate evidence. For multiallelic polymorphisms, it is common to group alleles together and analyze the data in the same way as for a biallelic polymorphism.

The first low-penetrance breast cancer susceptibility locus identified by the association approach was the HRAS1 minisatellite (8) . This has more than 30 alleles, of which 4 are common, whereas the rest, which have a combined frequency of 0.06, are classified as "rare." These rare alleles have been found to be associated with a 1.9-fold increased relative risk of breast cancer (and increased risk of other cancers) and are estimated to account for 9% of all breast cancer incidence. However, the molecular mechanism underlying this association remains unclear. The HRAS1 locus has been reviewed extensively (8 , 9) and so will not be considered further here.

Association studies have also been performed on other genes with putative involvement in breast cancer susceptibility. The candidate genes studies thus far can be divided into three main groups: genes for proteins with roles in steroid hormone metabolism; genes coding for carcinogen metabolism enzymes; and common alleles of genes that have been identified through family studies such as TP53 and BRCA1. The candidate gene polymorphisms reviewed here are listed in Table 1 .

	Steroid Hormone Metabolism Genes.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

The bioavailability of hormones is partially controlled by catabolism, and catechol estrogens (2 hydroxy-estrogens) are the major breakdown products of estrogens. COMT is a phase II enzyme that methylates catechol-estrogens during their conjugation and inactivation. It has two forms: one membrane-bound and the other cytosolic; both are expressed in breast tissue and share a polymorphism associated with differences in methylation activity.

The sex hormones control the activation of responsive genes by first binding to specific receptors and forming complexes that can in turn bind to sequences in the promoters of downstream, hormone-responsive genes. Thus, steroid hormone receptor genes, such as ER, PR, and AR, are candidates for breast cancer susceptibility genes.

	Carcinogen Metabolism Genes.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
Several enzymes have evolved for the detoxification of xenobiotic compounds, and their gene expression is induced in response to the presence of the compound (e.g., polycyclic aromatic hydrocarbons found in tobacco smoke). The actions of phase I and phase II enzymes render susceptible compounds more soluble and more readily excreted and ought to reduce cancer risk. However, the more soluble products of some compounds are even more potent carcinogens than the less soluble form. Hence, a genetic change that increases the expression of the gene or the activity of the protein produced may increase the amount of reactive carcinogen formed and, thus, increase the risk of cancer.

Two phase I enzymes, CYP1A1 and CYP2D6, are induced by, and act on, carcinogens found in tobacco smoke. Both have polymorphic differences in either inducibility or activity. CYP2E1, an enzyme that metabolizes ethanol, is also a candidate because epidemiological studies suggest that breast cancer risk is increased with alcohol consumption (11) .

The GST family are phase II enzymes that detoxify carcinogens and their reactive intermediates, such as those produced by CYP1A1, by facilitating their conjugation to glutathione and subsequent excretion. For both GSTM1 and GSTT1 [reviewed by Rebbeck (12) ], a high percentage of the Caucasian population are homozygous for null alleles (up to 60 and 20%, respectively) and have no detoxifying GST activity. Levels of DNA adducts, sister-chromatid-exchange, and somatic genetic mutations may be increased in carriers of GSTM1 and GSTT1 null genotypes (12) .

The N-acetyl transferases, NAT1 and NAT2, are also phase II enzymes, and they participate in the detoxification of the arylamines, some of the main carcinogenic components of tobacco smoke, and also the amines produced during the cooking of meat (13 , 14) . However, the action of NATs on these carcinogens can produce electrophilic ions that may induce point mutations in DNA. Polymorphism in both genes results in two phenotypes: slow acetylators who are homozygous for low-activity alleles, and fast acetylators who carry one or more high-activity alleles.

	Common Alleles of High-Penetrance Genes.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
Mutations in the TP53 and BRCA1 genes are associated with a high lifetime risk of breast and other cancers (15 , 16) . TP53 is a tumor suppressor gene whose protein is produced in response to DNA damage through radiation or genotoxic agents, resulting in cell cycle arrest in G₁ and induction of pathways leading to DNA repair or apoptosis. Mutation in the TP53 gene results in decreased p53 activity, which may lead to failure of cells with DNA damage to arrest and thus to continue to replicate with damaged DNA. In the case of BRCA1, where the protein function is still uncertain, the majority of confirmed mutations generate truncated proteins that are likely to have severely reduced activity. It has been hypothesized that amino acid substitutions outside the major functional domains may confer more moderate breast cancer risks. The majority of these substitutions are rare (17) , and putative functional effects remain unconfirmed. However, it has been possible to test empirically the risks associated with the common polymorphisms.

Some of the genes discussed above have been assessed in multiple studies, whereas attempts to replicate the findings of other studies have yet to be reported. Here we have attempted to identify all of the published reports. Because most of these are based on small sample sizes, we have combined the results where possible in meta-analyses to obtain more precise estimates of risk. We discuss the implications of these findings and highlight areas where further work could be carried out profitably.

	Materials and Methods

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
Literature Search.
Published studies were identified using the Medline (National Library of Medicine, Washington DC) and BIDS databases for 1983–July 1998, using the search terms "breast-neoplasms" and "polymorphism(s)." We also searched for studies on each specific candidate gene: for example, for CYP17 the terms "CYP17" and "breast neoplasm" were used. In addition, the bibliographies of studies identified by the electronic searches were hand searched. Eligible studies were those that compared genotypic or allele frequencies of candidate genes in a series of breast cancer cases with a series of non-breast cancer controls using genomic DNA. Studies in which tumor DNA was used from cases with genomic DNA from controls were excluded. Studies of HRAS alleles and breast cancer risk were also excluded because these have been reviewed extensively by other authors (8 , 9) .

Meta-analysis.
Whenever possible, raw data from comparable studies were analyzed jointly, using likelihood methods. Analyses were based on logistic regression and were carried out using the program S Plus. Each study was treated as a separate stratum, and the (control) allele or carrier frequencies in each study were permitted to be distinct, enabling studies with very different population frequencies to be considered jointly. For those metabolic polymorphisms associated with a specific phenotype, the principal analyses combined genotypes by phenotype classes (for example, poor metabolizer, slow acetylator). For all other polymorphisms, ORs were compared for each genotype. Genotype-specific ORs were estimated assuming that the genotype frequencies in controls were consistent with Hardy-Weinberg equilibrium (18) . Likelihood ratio tests (with degrees of freedom equal to number of genotypes - 1) were then used to test whether the ORs differed significantly from 1. If significant evidence of an association was found, a test for heterogeneity was performed. Ninety-five percent confidence intervals were calculated by direct examination of the likelihood surface. Joint analysis by subgroup (e.g., menopausal status) could only be performed if studies reported results for each subgroup. Specific analysis considering confounding factors such as age was not possible because raw data were not available.

	Results

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
We identified 46 eligible studies (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64) , which are listed in Table 2 . Although the basic study designs were all the same, a wide variety of sources of both cases and controls were used. Most reported studies were quite small: the median number of cases and controls combined was 391 (range, 58–1431).

	Steroid Hormone Metabolism Genes.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
The COMT Val158 Met polymorphism has been investigated in three studies. Thompson et al. (60) , found a significantly increased risk of premenopausal breast cancer in COMT^{Met carrier} women, with a nonsignificantly reduced risk of postmenopausal cancer. However, an earlier study had reported the opposite (although nonsignificant) effects for the same genotype, i.e., a reduced risk of premenopausal cancer and an increased risk of postmenopausal breast cancer (39) , and a third study found no effect in unselected cases (51) . Conflicting results have also been reported in four studies of the 1931TC polymorphism in the CYP17 promoter. Fiegelson et al. (30) found an increased risk of breast cancer for the CYP17^C carrier in a subgroup analysis of 40 advanced cases, a finding not confirmed in three other studies (29 , 35 , 62) . A possible role for CYP19 in breast cancer has been suggested by Haiman et al. (32) and Kristensen et al. (37) reported an increased risk for carriers of the (TTTA)₁₂ alleles; however, another group reported a statistically significant inverse association for this allele (55) , and our own unpublished data have failed to confirm a significant risk (65) . Haiman et al. also found a significantly increased risk for carriers of the rare (TTTA)₁₀ allele (32) , but again this finding has not been confirmed by others (55 , 65) . Of two studies of the estrogen receptor gene polymorphism, CCC325CCG, one found a significantly elevated risk for the G carrier (42) , but a subsequent, larger study failed to confirm this result (58) .

	Carcinogen Metabolism Genes.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
One or more of four different polymorphisms in CYP1A1 have been assessed in four different studies, two of which have investigated the role of these polymorphisms in Caucasians and African Americans separately. The only significant result reported was in the study of Taioli et al. (59) , who found an increased breast cancer risk for African-American women who were CC homozygote for the 3'UTR TC (T6235C). In contrast, the other study of African-American women found a nonsignificantly reduced breast cancer risk associated with this genotype (23) . Of five studies of the GSTM1 gene deletion, only one found that null individuals were at significantly increased risk (34) , and in subgroup analysis, this effect was restricted to postmenopausal breast cancer. Charrier et al. (26) also found a significantly increased risk of breast cancer in the subgroup of patients diagnosed over the age of 50.

	Other Genes.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
A significant effect of the Arg72Pro polymorphism in TP53 has been reported by Sjalander et al. (56) , who found that TP53^Arg/Pro heterozygotes were at increased risk, as were TP53^Pro carriers. Pro homozygotes were also at increased risk, although the confidence intervals were wide and the effect was not statistically significant. Two other studies of the same polymorphism had found no significant effect (43 , 61) . The genes HSP-70 and TNF- have been investigated by one group, which found significantly increased risk for rare allele carriers of both genes (see Table 3 ). However, this study was small, and their results have not been confirmed or refuted by other groups.

	Meta-analysis.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
Comparable data from more than one study that could be combined were available for 25 different combinations of polymorphism and patient subgroups. The results of these analyses are given in Table 4 . Statistically significant differences in genotype frequencies were found in three case-control comparisons of unselected cases. These were for CYP19 (TTTA)_n polymorphism [(TTTA)₁₀ carrier OR = 2.33; P = 0.002], the GSTP1 Ile105Val polymorphism (Val carrier OR = 1.60; P = 0.02), and the TP53 Arg72Pro (Pro carrier OR = 1.27; P = 0.03). In addition, the GSTM1 gene deletion was found to be significant in postmenopausal breast cancer (null homozygote OR = 1.33; P = 0.04). There was also some evidence that homozygotes for the PR PROGINS allele are protected against breast cancer, although this result was of borderline statistical significance.

	Gene-Environment Interaction.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

Lavigne et al. (39) looked for interactions between the Val158 Met polymorphism in the COMT gene and several factors including family history, menopausal status, smoking, alcohol, oral contraceptive use, and hormone replacement therapy. Helzlsouer et al. (34) also explored the possibility of interactions between GSTM1, GSTP1, and GSTT1 genotypes with family history, hormone replacement therapy, cigarette smoking, alcohol consumption, and body mass index. Although no overall effect was found in either study, both reported interactions with menopausal status and body mass index, and Helzlsouer et al. (34) additionally noted an interaction between GSTT1 and alcohol consumption. However, no studies attempting to confirm these quite complex interactions have yet been published.

	Gene-Gene Interaction.

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
The possibility of gene-gene interactions have rarely been explored. One small study carried out genotyping in three genes: CYP1A1, GSTM1, and GSTT1 (23) . No interaction between these genes was found. The studies of Helzlsouer et al. (34) on the GST genes and Lavigne et al. (39) on COMT were carried out on the same populations. The increased relative risk of postmenopausal breast cancer for GSTM1^Null and GSTP1^Ile/Val/GSTP1^Val/Val women of around 2 was found to be increased to a 3–4-fold increased risk if they were also COMT^Met/Met. Again, no confirmatory studies have yet been published.

	Discussion

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 
We have found a substantial number of reports of studies that have investigated candidate genes for low-penetrance breast cancer susceptibility alleles. Despite this research effort, there is no clear evidence that any of these polymorphisms are strongly associated with breast cancer risk. Of the individual studies, few of the reported associations have been statistically significant, and no significant association has been reported by more than one study. In some cases, this might be due to a lack of statistical power in individual studies. Even among the significant associations, the magnitude of the effect found is rarely greater than 2.5-fold increased risk. If the rare allele frequency is 0.2, 315 cases and 315 controls would be required to detect this magnitude of risk for a rare allele homozygote with 90% power at the 5% significance level: 10 of the 46 studies reported were larger than this.

We have attempted to reduce this lack of power by combining results in meta-analyses, but even the results of these need to be interpreted with some caution. Of the 25 associations tested in at least two studies, 4 were significant at the 5% level. One of these was significant only in a subgroup of cases (postmenopausal) and was not significant overall. Such subgroup-specific associations must always be treated with caution given that there is no clear a priori reason to suspect a subgroup effect. Moreover, only one of the associations has a significance levels of <1%. Given the number of polymorphisms being tested, a significance level of 10^-4 or smaller would be required to provide strong evidence.

In any systematic review, a major cause for concern is the potential for publication bias. The most common scenario is the nonpublication of negative studies (i.e., those finding no significant association), resulting in bias of any meta-analysis away from the null. We cannot exclude this possibility for the three polymorphisms with significant results in the meta-analyses. For the polymorphisms for which we have found no evidence for an association between genotype and breast cancer risk, it is possible, but unlikely, that bias toward the null has occurred. There is an urgent need for databases into which the results of all association studies (positive and negative) with candidate genes can be entered to minimize the effects of publication bias.

Consistency of reporting added further complications to the meta-analysis; many studies do not describe the ethnicity of their study populations; therefore, we have combined samples on the assumption that any variant studied will have the same effect in all populations. This assumption may only be valid if the variant studied is truly functional with respect to breast cancer risk. If the variant is simply a neutral marker for some other functional variant, the assumption may be invalid because linkage disequilibrium relationships often differ between populations. In addition, there is no consensus nomenclature for SNPs: early reports often described the restriction enzyme site involved, but there are instances of multiple polymorphisms detected by the same restriction enzyme within a single gene (e.g., there are two polymorphisms creating MspI sites in CYP1A1). More recent studies usually identify the base substitution, but in introns and UTRs of genes, this can also be arbitrary. In Table 1 , we presented the SNP and its general position (e.g., exon 3, intron 6, 3'UTR) for clarity, but workers will need to refer to the original articles for sufficient detail to replicate the DNA assays. The requirement for public databases of SNPs has recently been recognized (66) , and it is hoped these will then provide a standardized description. Furthermore, methodological difficulties have been caused by genes having several different polymorphisms in linkage disequilibrium with one another. For example, CYP1A1 has two SNPs in strong linkage disequilibrium with one another; these are the exon 7 Ile462Val and the 3'UTR TC (T6253C) SNPs. Both have been shown to be significantly associated with risk of some neoplasms (although not breast cancer), but combining them in a meta-analysis would require a somewhat more complicated analytical approach.

Several studies have reported on putative gene-gene and gene-environment interactions. The results of these analyses should, however, be treated with caution. The problem of post hoc subgroup analyses and multiple hypothesis testing renders the interpretation of positive results difficult. Negative results also should be treated with caution because few studies will have had sufficient power to detect moderate interaction effects. For example, 1500 cases and 1500 controls would be required to detect an interaction between two genotypes each with a frequency of 0.1 and a relative risk of 1.1 but with a relative risk of 2.5 when combined. These analyses should, therefore, be treated as hypothesis generating rather than hypothesis testing.

Despite these concerns, we believe some firm conclusions can be drawn. For several polymorphisms, the best estimate of risk either from the individual studies or the combined meta-analyses is sufficiently precise to exclude a relative risk of 1.5. These include the polymorphisms in BRCA1, COMT, CYP17, CYP1A1, NAT1, and NAT2. This does not necessarily imply that a negligible fraction of breast cancer incidence is attributable to such genes. For example, the upper confidence interval for the CYP17 effect (1.39) would still correspond to a population-attributable fraction of 20%. We have, however, concluded that these polymorphisms contribute little to the familial aggregation of breast cancer: the same effect would correspond to a relative risk to siblings of cases of 1.01 [for details of calculation, see Easton (67) ], whereas epidemiological studies have found the relative risk to be 2-fold.

For other polymorphisms, the risk estimates, although nonsignificant, are insufficiently precise to exclude a moderate risk (>1.5), and larger studies are needed to obtain more precise risk estimates. These include polymorphisms in EDH17B2, ER, CYP2D6, CYP2E1, GSTT1, HSP70, PR, and TNF. Finally, the polymorphisms in CYP19, GSTM1, GSTP1, and TP53 appear to be stronger candidates for low-penetrance breast cancer susceptibility genes, although they too need to be confirmed in larger studies. It is more likely, however, that the majority in variation in susceptibility to breast cancer is due to genes that have yet to be identified or tested. Candidate genes include those involved in DNA repair and micro- and macronutrient metabolism. In addition, gene-gene and gene-environment interactions may be important determinants of breast cancer risk. Such interactions would produce substantially increased risks in individuals with the right combination of factors, but large studies would be required to elucidate these effects. Further work is clearly needed to address these issues, but these studies will need to be substantially larger than the association studies published to date.

	Acknowledgments

 
We thank Katie Blyth (Department of Pathology, University of Cambridge) for help in obtaining references.

	Footnotes

¹ This work was supported by the Cancer Research Campaign (CRC). B. A. J. P. is a Gibb Fellow of the Cancer Research Campaign.

² These authors contributed equally to this study.

³ To whom requests for reprints should be addressed, at CRC Human Cancer Genetics Group, University Department of Oncology, Strangeways Research Laboratories, Worts Causeway, Cambridge CB1 8RN, UK.

⁴ The abbreviations used are: SNP, single nucleotide polymorphism; OR, odds ratio; COMT, catechol-O-methyltransferase; GST, glutathione-S-transferase; NAT, N-acetyl transferase; UTR, untranslated region.

Received 12/ 3/98; revised 6/22/99; accepted 7/12/99.

	References

Top Abstract Introduction Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Common Alleles of High... Materials and Methods Results Steroid Hormone Metabolism... Carcinogen Metabolism Genes. Other Genes. Meta-analysis. Gene-Environment Interaction. Gene-Gene Interaction. Discussion References

 

1. Pharoah P. D. P., Mackay J. Absolute risk of breast cancer in women at increased risk: a more useful clinical measure than relative risk?. Breast, 7: 255-259, 1998.
2. National Cancer Institute. SEER Cancer Statistics Review, 1973–1995 National Cancer Institute Bethesda, MD 1999.
3. Newman B., Austin M. A., Lee M. Inheritance of human breast cancer: evidence for autosomal dominant transmission in high risk families. Proc. Natl. Acad. Sci. USA, 85: 3044-3048, 1988.[Abstract/Free Full Text]
4. Pharoah P. D. P., Day N. E., Duffy S., Easton D. F., Ponder B. A. J. Family history and the risk of breast cancer: a systematic review and meta-analysis. Int. J. Cancer, 71: 800-809, 1997.[Medline]
5. Peto J., Easton D. F., Matthews F. E., Ford D., Swerdlow A. J. Cancer mortality in relatives of women with breast cancer: the OPCS study. Int. J. Cancer, 65: 273-283, 1996.
6. Khoury M. J. Genetic epidemiology Rothman K. Greenland S. eds. . Modern Epidemiology, : 609-622, Lippincott-Raven New York 1997.
7. Risch N., Merikangas K. The future of genetic studies of complex diseases. Science (Washington DC), 273: 1516-1517, 1996.[Abstract/Free Full Text]
8. Krontiris T. G., Devlin B., Karp D. D., Robert N. J., Risch N. An association between the risk of cancer and mutations in the HRAS1 minisatellite locus. N. Engl. J. Med., 329: 517-523, 1993.[Abstract/Free Full Text]
9. Weston A., Godbold J. H. Polymorphisms of H-ras-1 and p53 in breast cancer and lung cancer: a meta-analysis. Environ. Health Perspect., 105 (Suppl 4): 919-926, 1997.
10. Kelsey J. L., Gammon M. D., John E. M. Reproductive factors and breast cancer. Epidemiol. Rev., 15: 36-47, 1993.[Free Full Text]
11. Hunter D. J., Willett W. C. Nutrition and breast cancer. Cancer Causes & Control, 7: 56-68, 1996.[Medline]
12. Rebbeck T. R. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer. Epidemiol., 6: 733-743, 1997.[Abstract/Free Full Text]
13. Hein D. W., Doll M. A., Rustan T. D., Gray K., Feng Y., Ferguson R. J., Grant D. M. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis (Lond.), 14: 1633-1638, 1993.[Abstract/Free Full Text]
14. Badawi A. F., Hirvonen A., Bell D. A., Lang N. P., Kadlubar F. F. Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen- DNA adduct formation in the human urinary bladder. Cancer Res., 55: 5230-5237, 1995.[Abstract/Free Full Text]
15. Shattuck-Eidens D., McClure M., Simard J., Labrie F., Narod S., Couch F., Hoskins K., Weber B., Castilla L., Erdos M. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. JAMA, 273: 535-541, 1995.
16. Børresen A. L., Andersen T. I., Garber J., Barbier-Piraux N., Thorlacius S., Eyfjörd J., Ottestad L., Smith-Sørensen B., Hovig E., Malkin D., Freind S. H. Screening for germ line TP53 mutations in breast cancer patients. Cancer Res., 52: 3234-3236, 1992.[Abstract/Free Full Text]
17. Friend S., Børresen A. L., Brody L., Casey G., Devilee P., Gayther S., Goldgar D., Murphy P., Weber B. L., Wiseman R. Breast cancer information on the web. Nat. Genet., 11: 238-239, 1995.[Medline]
18. Lathrop G. Estimating genotype relative risks. Tissue Antigens, 22: 160-166, 1983.[Medline]
19. Agundez J. A. G., Ladero J. M., Olivera M., Roman J. M., Benitez J. Genetic analysis of the arylamine N-acetyl transferase polymorphism in breast cancer patients. Oncology, 52: 7-11, 1995.[Medline]
20. Ambrosone C. B., Freudenheim J. L., Graham S., Marshall J. R., Vena J. E., Brasure J. R., Laughlin R., Nemoto T., Michalek A. M., Harrington A., Ford T. D., Shields P. G. Cytochrome P4501A1 and glutathione S-transferase (M1) polymorphisms and postmenopausal breast cancer risk. Cancer Res., 55: 3483-3485, 1995.[Abstract/Free Full Text]
21. Ambrosone C. B., Freudenheim J. L., Graham S., Marshall J. R., Vena J. E., Brasure J. R., Michalek A. M., Laughlin R., Nemoto T., Gillenwater K. A., Shields P. G. Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk. JAMA, 276: 1494-1501, 1996.[Abstract/Free Full Text]
22. Andersen T. I., Heimdal K. R., Skrede M., Tveit K., Berg K., Børresen A. L. Oestrogen receptor (ESR) polymorphisms and breast cancer susceptibility. Hum. Genet., 94: 665-670, 1994.[Medline]
23. Bailey L. R., Roodi N., Verrier C. S., Yee C. J., Dupont W. D., Parl F. F. Breast cancer and CYPIA1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res., 58: 65-70, 1998.[Abstract/Free Full Text]
24. Buchert E. T., Woosley R. L., Swain S. M., Oliver S. J., Coughlin S. S., Pickle L., Trock B., Riegel A. T. Relationship of CYP2D6 (debrisoquine hydroxylase) genotype to breast cancer susceptibility. Pharmacogenetics, 3: 322-327, 1993.[Medline]
25. Campbell I. G., Eccles D. M., Dunn B., Davis M., Leake V. p53 polymorphism in ovarian and breast cancer. Lancet, 347: 393-394, 1996.[Medline]
26. Charrier J., Maugard C. M., Le Mevel B., Bignon Y. J. Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility. Br. J. Cancer, 79: 346-353, 1999.[Medline]
27. Chouchane L., Ahmed S. B., Baccouche S., Remadi S. Polymorphism in the tumor necrosis factor- promotor region and in the heat shock protein 70 genes associated with malignant tumors. Cancer (Phila.), 80: 1489-1496, 1997.[Medline]
28. Dunning A. M., Chiano M., Smith N. R., Dearden J., Gore M., Oakes S., Wilson C., Stratton M., Peto J., Easton D., Clayton D., Ponder B. A. Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. Hum. Mol. Genet., 6: 285-289, 1997.[Abstract/Free Full Text]
29. Dunning A. M., Healey C. S., Pharoah P. D. P., Foster N., Easton D. F., Day N. E., Ponder B. A. J. Polymorphism in the steroid metabolism gene CYP17 and risk of breast cancer. Br. J. Cancer, 77: 2045-2047, 1998.[Medline]
30. Feigelson H. S., Coetzee G. A., Kolonel L. N., Ross R. K., Henderson B. E. A polymorphism in the CYP17 gene increases the risk of breast cancer. Cancer Res., 57: 1063-1065, 1997.[Abstract/Free Full Text]
31. Garrett E., Rowe S. M., Coughlan S. J., Horan R., McLinden J., Carney D. N., Fanning M., Kieback D. G., Headon D. R. Mendelian inheritance of a TaqI restriction fragment length polymorphism due to an insertion in the human progesterone receptor gene and its allelic imbalance in breast cancer. Cancer Res. Ther. Control, 4: 217-222, 1995.
32. Haiman C. A., Hankinson S. E., Speizer F. E., Hunter D. J. A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Proc. Am. Assoc. Cancer Res., 40: 194 1999.
33. Harries L. W., Stubbins M. J., Forman D., Howard G. C. W., Wolf C. R. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis (Lond.), 18: 641-644, 1997.[Abstract/Free Full Text]
34. Helzlsouer K. J., Selmin O., Huang H-Y., Strickland P. T., Hoffman S., Alberg A. J., Watson M., Comstock G. W., Bell D. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J. Natl. Cancer Inst., 90: 512-518, 1998.[Abstract/Free Full Text]
35. Helzlsouer K. J., Huang H-Y., Strickland P. T., Hoffman S., Alberg A. J., Comstock G. W., Bell D. A. Association between CYP17 polymorphism and the development of breast cancer. Cancer Epidemiol., Biomarkers & Prev., 7: 945-949, 1998.[Abstract]
36. Huober J., Bertram B., Petru E., Kaufmann M., Schmahl D. Metabolism of debrisoquine and susceptibility to breast cancer. Breast Cancer Res. Treat., 18: 43-48, 1991.[Medline]
37. Kristensen V. N., Andersen T. I., Lindblom A., Erikstein B., Magnus P., Børresen-Dale A. L. A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics, 8: 43-48, 1998.[Medline]
38. Lancaster J. M., Berchuck A., Carney M. E., Wiseman R., Taylor J. A. Re: "Progesterone receptor gene polymorphism and risk for breast and ovarian cancer.". Br. J. Cancer, 78: 277 1998.
39. Lavigne J. A., Helzlsouer K. J., Huang H-Y., Strickland P. T., Bell D. A., Selmin O., Watson M. A., Hoffman S., Comstock G. W., Yager J. D. An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. Cancer Res., 57: 5493-5497, 1997.[Abstract/Free Full Text]
40. Hunter D. J., Hankinson S. E., Hough H., Gertig D. M., Garcia Closas M., Spiegelman D., Manson J. E., Colditz G. A., Willett W. C., Speizer F. E., Kelsey K. A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. Carcinogenesis (Lond.), 18: 2127-2132, 1997.[Abstract/Free Full Text]
41. Ishibe N., Hankinson S. E., Colditz G. A., Spiegelman D., Willett W. C., Speizer F. E., Kelsey K. T., Hunter D. J. Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses’ Health Study. Cancer Res., 58: 667-671, 1998.[Abstract/Free Full Text]
42. Iwase H., Greenman J. M., Barnes D. M., Hodgson S., Bobrow L., Mathew C. G. Sequence variants of the estrogen receptor (ER) gene found in breast cancer patients with ER negative and progesterone receptor positive tumors. Cancer Lett., 108: 179-184, 1996.[Medline]
43. Kawajiri K., Nakachi K., Imai K., Watanabe J., Hayashi S. Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis (Lond.), 14: 1085-1089, 1993.[Abstract/Free Full Text]
44. Kelsey K. T., Hankinson S. E., Colditz G. A., Springer K., Garcia-Closas M., Spiegelman D., Manson J. E., Garland M., Stampfer M. J., Willett W. C., Speizer F. E., Hunter D. J. Glutathione S-transferase class µ deletion polymorphism and breast cancer: results from prevalent versus incident cases. Cancer Epidemiol., Biomarkers & Prev., 6: 511-515, 1997.[Abstract]
45. Ladero J. M., Benitez J., Jara C., Llerena A., Valdivielso M. J., Munoz J. J., Vargas E. Polymorphic oxidation of debrisoquine in women with breast cancer. Oncology, 48: 107-110, 1991.[Medline]
46. Ladona M. G., Abildua R. E., Ladero J. M., Roman J. M., Plaza M. A., Agundez J. A., Munoz J. J., Benitez J. CYP2D6 genotypes in Spanish women with breast cancer. Cancer Lett., 99: 23-28, 1996.[Medline]
47. Mannermaa A., Peltoketo H., Winqvist R., Ponder B. A. J., Kiviniemi H., Easton D. F., Poutanen M., Isomaa V., Vihko R. Human familial and sporadic breast cancer: analysis of the coding regions of the 17ß-hydroxysteroid dehydrogenase 2 gene (EDH17B2) using a single-strand conformation polymorphism assay. Hum. Genet., 93: 319-324, 1994.[Medline]
48. Manolitsas T. P., Englefield P., Eccles D. M., Campbell I. G. Re: "No association of a 306-bp insertion polymorphism in the progesterone receptor gene with ovarian and breast cancer.". Br. J. Cancer, 75: 1398-1399, 1997.[Medline]
49. Mavridou D., Gornall R., Campbell I. G., Eccles D. M. TP53 intron 6 polymorphism and the risk of ovarian and breast cancer. Br. J. Cancer, 77: 676-677, 1998.[Medline]
50. Millikan R. C., Pittman G. S., Newman B., Tse C. K., Selmin O., Rockhill B., Savitz D., Moorman P. G., Bell D. A. Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol., Biomarkers & Prev., 7: 371-378, 1998.[Abstract/Free Full Text]
51. Millikan R. C., Pittman G. S., Tse C. K., Duell E., Newman B., Savitz D., Moorman P. G., Boissy R. J., Bell D. A. Catechol-O-methyltransferase and breast cancer risk. Carcinogenesis (Lond.), 19: 1943-1947, 1998.[Abstract/Free Full Text]
52. Peller S., Kopilova Y., Slutzki S., Halevy A., Kvitko K., Rotter V. A novel polymorphism in intron 6 of the human p53 gene: a possible association with cancer predisposition and susceptibility. DNA Cell Biol., 14: 983-990, 1995.[Medline]
53. Pontin J. E., Hamed H., Fentiman I. S., Idle J. R. Cytochrome p450dbl phenotypes in malignant and benign breast disease. Eur. J. Cancer, 26: 790-792, 1998.
54. Shields P. G., Ambrosone C. B., Graham S., Bowman E. D., Harrington A. M., Gillenwater K. A., Marshall J. R., Vena J. E., Laughlin R., Nemoto T., Freudenheim J. L. A cytochrome P4502E1 genetic polymorphism and tobacco smoking in breast cancer. Mol. Carcinog., 17: 144-150, 1996.[Medline]
55. Siegelmann-Danieli N., Buetow K. H. Constitutional genetic variation at the human aromatase gene (Cyp19) and breast cancer risk. Br. J. Cancer, 79: 456-463, 1999.[Medline]
56. Sjalander A., Birgander R., Hallmans G., Cajander S., Lenner P., Athlin L., Beckman G., Beckman L. p53 polymorphisms and haplotypes in breast cancer. Carcinogenesis (Lond.), 17: 1313-1316, 1996.[Abstract/Free Full Text]
57. Smith C. A., Moss J. E., Gough A. C., Spurr N. K., Wolf C. R. Molecular genetic analysis of the cytochrome P450-debrisoquine hydroxylase locus and association with cancer susceptibility. Environ. Health Perspect., 98: 107-112, 1992.[Medline]
58. Southey M. C., Batten L. E., McCredie M. R. E., Giles G. C., Dite G., Hopper J. L., Venter D. J. Estrogen receptor polymorphism at codon 325 and risk of breast cancer in women before age forty. J. Natl. Cancer Inst., 90: 533-536, 1998.
59. Taioli E., Trachman J., Chen X., Toniolo P., Garte S. J. A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res., 55: 3757-3758, 1995.[Abstract/Free Full Text]
60. Thompson P. A., Shields P. G., Fruedenheim J. L., Stone A., Vena J. E., Marshall J. R., Graham S., Laughlin R., Nemoto T., Kadlubar F. F., Ambrosone C. B. Genetic polymorphisms in catechol-O-methyltransferase, menopausal status and breast cancer risk. Cancer Res., 58: 2107-2110, 1998.[Abstract/Free Full Text]
61. Wang-Gohrke S., Rebbeck T. R., Besenfelder W., Kreienberg R., Runnebaum I. B. p53 germline polymorphisms are associated with an increased risk for breast cancer in German women. Anticancer Res., 18: 2095-2099, 1998.[Medline]
62. Weston A., Pan C-F., Bleiweiss I. J., Ksieski H. B., Roy N., Maloney N., Wolff M. S. CYP17 genotype and breast cancer risk. Cancer Epidemiol., Biomarkers & Prev., 7: 941-944, 1998.[Abstract]
63. Zheng W., Deitz A. C., Campbell D. R., Wen W. Q., Cerhan J. R., Sellers T. A., Folsom A. R., Hein D. W. N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk. Cancer Epidemiol., Biomarkers & Prev., 8: 233-239, 1999.[Abstract/Free Full Text]
64. Zhong S., Wyllie A. H., Barnes D., Wolf C. R., Spurr N. K. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis (Lond.), 14: 1821-1824, 1993.[Abstract/Free Full Text]
65. Healey, C. S., Dunning, A. M., Durocher, F., Teare, D., Easton, D. F., and Ponder, B. A. J. Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk. Carcinogenesis (Lond.), in press, 1999.
66. Collins F. S., Guyer M. S., Charkravarti A. Variations on a theme: cataloging human DNA sequence variation. Science (Washington DC), 278: 1580-1581, 1997.[Free Full Text]
67. Easton D. F. Cancer risks in A-T heterozygotes. Int. J. Radiat. Biol., 66: S177-S182, 1994.[Medline]

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				N. A. Kocabas, S. Sardas, S. Cholerton, A. K. Daly, and A. E. Karakaya N-Acetyltransferase (NAT2) Polymorphism and Breast Cancer Susceptibility: A Lack of Association in a Case-Control Study of Turkish Population International Journal of Toxicology, January 1, 2004; 23(1): 25 - 31. [Abstract] [Full Text] [PDF]

				N. Moullan, D. G. Cox, S. Angele, P. Romestaing, J.-P. Gerard, and J. Hall Polymorphisms in the DNA Repair Gene XRCC1, Breast Cancer Risk, and Response to Radiotherapy Cancer Epidemiol. Biomarkers Prev., November 1, 2003; 12(11): 1168 - 1174. [Abstract] [Full Text]

				F. Sata, H. Yamada, A. Yamada, E. H. Kato, S. Kataoka, Y. Saijo, T. Kondo, J. Tamaki, H. Minakami, and R. Kishi A polymorphism in the CYP17 gene relates to the risk of recurrent pregnancy loss Mol. Hum. Reprod., November 1, 2003; 9(11): 725 - 728. [Abstract] [Full Text] [PDF]

				J. H. Fowke, F.-L. Chung, F. Jin, D. Qi, Q. Cai, C. Conaway, J.-R. Cheng, X.-O. Shu, Y.-T. Gao, and W. Zheng Urinary Isothiocyanate Levels, Brassica, and Human Breast Cancer Cancer Res., July 15, 2003; 63(14): 3980 - 3986. [Abstract] [Full Text] [PDF]

				R. Wooster and B. L. Weber Breast and Ovarian Cancer N. Engl. J. Med., June 5, 2003; 348(23): 2339 - 2347. [Full Text] [PDF]

				Y.-P. Fu, J.-C. Yu, T.-C. Cheng, M. A. Lou, G.-C. Hsu, C.-Y. Wu, S.-T. Chen, H.-S. Wu, P.-E. Wu, and C.-Y. Shen Breast Cancer Risk Associated with Genotypic Polymorphism of the Nonhomologous End-Joining Genes: A Multigenic Study on Cancer Susceptibility Cancer Res., May 15, 2003; 63(10): 2440 - 2446. [Abstract] [Full Text] [PDF]

				B. A. Nexo, U. Vogel, A. Olsen, T. Ketelsen, Z. Bukowy, B. L. Thomsen, H. Wallin, K. Overvad, and A. Tjonneland A specific haplotype of single nucleotide polymorphisms on chromosome 19q13.2-3 encompassing the gene RAI is indicative of post-menopausal breast cancer before age 55 Carcinogenesis, May 1, 2003; 24(5): 899 - 904. [Abstract] [Full Text] [PDF]

				B. F. El-Rayes, S. Ali, L. K. Heilbrun, S. Lababidi, D. Bouwman, D. Visscher, and P. A. Philip Cytochrome P450 and Glutathione Transferase Expression in Human Breast Cancer Clin. Cancer Res., May 1, 2003; 9(5): 1705 - 1709. [Abstract] [Full Text] [PDF]

				E. Ziv, J. Shepherd, R. Smith-Bindman, and K. Kerlikowske Mammographic Breast Density and Family History of Breast Cancer J Natl Cancer Inst, April 2, 2003; 95(7): 556 - 558. [Abstract] [Full Text] [PDF]

				B. Faraglia, S. Y. Chen, M. D. Gammon, Y. Zhang, S. L. Teitelbaum, A. I. Neugut, H. Ahsan, G. C. Garbowski, H. Hibshoosh, D. Lin, et al. Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke Carcinogenesis, April 1, 2003; 24(4): 719 - 725. [Abstract] [Full Text] [PDF]

				M. Ishitobi, Y. Miyoshi, A. Ando, S. Hasegawa, C. Egawa, Y. Tamaki, M. Monden, and S. Noguchi Association of BRCA2 Polymorphism at Codon 784 (Met/Val) with Breast Cancer Risk and Prognosis Clin. Cancer Res., April 1, 2003; 9(4): 1376 - 1380. [Abstract] [Full Text] [PDF]

				N. E. Caporaso Why Have We Failed to Find the Low Penetrance Genetic Constituents of Common Cancers? Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1544 - 1549. [Full Text] [PDF]

				M. M. de Jong, I. M. Nolte, G. J. te Meerman, W. T. A. van der Graaf, E. G. E. de Vries, R. H. Sijmons, R. M. W. Hofstra, and J. H. Kleibeuker Low-penetrance Genes and Their Involvement in Colorectal Cancer Susceptibility Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1332 - 1352. [Abstract] [Full Text] [PDF]

				P. Greenwald Cancer Prevention Clinical Trials J. Clin. Oncol., September 15, 2002; 20(90001): 14s - 22. [Abstract] [Full Text] [PDF]

				Z. Ye and J. M. Parry Concerning the CYP17 MSPA1 polymorphism and breast cancer risk: a meta-analysis Mutagenesis, September 1, 2002; 17(5): 447 - 448. [Full Text] [PDF]

				A. Forsti, Q. Jin, E. Grzybowska, M. Soderberg, H. Zientek, M. Sieminska, J. Rogozinska-Szczepka, E. Chmielik, B. Utracka-Hutka, and K. Hemminki Sex hormone-binding globulin polymorphisms in familial and sporadic breast cancer Carcinogenesis, August 1, 2002; 23(8): 1315 - 1320. [Abstract] [Full Text] [PDF]

				H Tulinius, G H Olafsdottir, H Sigvaldason, A Arason, R B Barkardottir, V Egilsson, H M Ogmundsdottir, L Tryggvadottir, S Gudlaugsdottir, and J E Eyfjord The effect of a single BRCA2 mutation on cancer in Iceland J. Med. Genet., July 1, 2002; 39(7): 457 - 462. [Abstract] [Full Text] [PDF]

				E. L. Goode, A. M. Dunning, B. Kuschel, C. S. Healey, N. E. Day, B. A. J. Ponder, D. F. Easton, and P. P. D. Pharoah Effect of Germ-Line Genetic Variation on Breast Cancer Survival in a Population-based Study Cancer Res., June 1, 2002; 62(11): 3052 - 3057. [Abstract] [Full Text] [PDF]

				K. L. Nathanson, Y. Y. Shugart, R. Omaruddin, C. Szabo, D. Goldgar, T. R. Rebbeck, and B. L. Weber CGH-targeted linkage analysis reveals a possible BRCA1 modifier locus on chromosome 5q Hum. Mol. Genet., May 16, 2002; 11(11): 1327 - 1332. [Abstract] [Full Text] [PDF]

				M M de Jong, I M Nolte, G J te Meerman, W T A van der Graaf, J C Oosterwijk, J H Kleibeuker, M Schaapveld, and E G E de Vries Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility J. Med. Genet., April 1, 2002; 39(4): 225 - 242. [Abstract] [Full Text] [PDF]

				Z. Ye and J. M. Parry The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis Mutagenesis, March 1, 2002; 17(2): 119 - 126. [Abstract] [Full Text] [PDF]

				P. F. Firozi, M. L. Bondy, A. A. Sahin, P. Chang, F. Lukmanji, E. S. Singletary, M. M. Hassan, and D. Li Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer Carcinogenesis, February 1, 2002; 23(2): 301 - 306. [Abstract] [Full Text] [PDF]

				B. L. Powell, I. L. van Staveren, P. Roosken, F. Grieu, E. M.J.J. Berns, and B. Iacopetta Associations between common polymorphisms in TP53 and p21WAF1/Cip1 and phenotypic features of breast cancer Carcinogenesis, February 1, 2002; 23(2): 311 - 315. [Abstract] [Full Text] [PDF]

				M. Zhao, R. Lewis, D. R. Gustafson, W.-Q. Wen, J. R. Cerhan, and W. Zheng No Apparent Association of GSTP1 A313G Polymorphism with Breast Cancer Risk among Postmenopausal Iowa Women Cancer Epidemiol. Biomarkers Prev., December 1, 2001; 10(12): 1301 - 1302. [Full Text] [PDF]

				K. Gudmundsdottir, L. Tryggvadottir, and J. E. Eyfjord GSTM1, GSTT1, and GSTP1 Genotypes in Relation to Breast Cancer Risk and Frequency of Mutations in the p53 Gene Cancer Epidemiol. Biomarkers Prev., November 1, 2001; 10(11): 1169 - 1173. [Abstract] [Full Text] [PDF]

				C. B. Ambrosone, C. Sweeney, B. F. Coles, P. A. Thompson, G. Y. McClure, S. Korourian, M. Y. Fares, A. Stone, F. F. Kadlubar, and L. F. Hutchins Polymorphisms in Glutathione S-Transferases (GSTM1 and GSTT1) and Survival after Treatment for Breast Cancer Cancer Res., October 1, 2001; 61(19): 7130 - 7135. [Abstract] [Full Text] [PDF]

				Y. Giguere, E. Dewailly, J. Brisson, P. Ayotte, N. Laflamme, A. Demers, V.-I. Forest, S. Dodin, J. Robert, and F. Rousseau Short Polyglutamine Tracts in the Androgen Receptor Are Protective against Breast Cancer in the General Population Cancer Res., August 1, 2001; 61(15): 5869 - 5874. [Abstract] [Full Text] [PDF]

				C. A. Haiman, M. J. Stampfer, E. Giovannucci, J. Ma, N. E. Decalo, P. W. Kantoff, and D. J. Hunter The Relationship between a Polymorphism in CYP17 with Plasma Hormone Levels and Prostate Cancer Cancer Epidemiol. Biomarkers Prev., July 1, 2001; 10(7): 743 - 748. [Abstract] [Full Text] [PDF]

				E. Ziv, J. Cauley, P. A. Morin, R. Saiz, and W. S. Browner Association Between the T29->C Polymorphism in the Transforming Growth Factor {beta}1 Gene and Breast Cancer Among Elderly White Women: The Study of Osteoporotic Fractures JAMA, June 13, 2001; 285(22): 2859 - 2863. [Abstract] [Full Text] [PDF]

				K. Armstrong Genetic Susceptibility to Breast Cancer: From the Roll of the Dice to the Hand Women Were Dealt JAMA, June 13, 2001; 285(22): 2907 - 2909. [Full Text] [PDF]

				K. Mitrunen, N. Jourenkova, V. Kataja, M. Eskelinen, V.-M. Kosma, S. Benhamou, D. Kang, H. Vainio, M. Uusitupa, and A. Hirvonen Polymorphic Catechol-O-methyltransferase Gene and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., June 1, 2001; 10(6): 635 - 640. [Abstract] [Full Text] [PDF]

				C. A. Haiman, S. E. Hankinson, G. A. Colditz, D. J. Hunter, and I. De Vivo A Polymorphism in CYP17 and Endometrial Cancer Risk Cancer Res., May 1, 2001; 61(10): 3955 - 3960. [Abstract] [Full Text]

				K. L. Nathanson and B. L. Weber 'Other' breast cancer susceptibility genes: searching for more holy grail Hum. Mol. Genet., April 1, 2001; 10(7): 715 - 720. [Abstract] [Full Text] [PDF]

				K. Mitrunen, N. Jourenkova, V. Kataja, M. Eskelinen, V.-M. Kosma, S. Benhamou, H. Vainio, M. Uusitupa, and A. Hirvonen Glutathione S-Transferase M1, M3, P1, and T1 Genetic Polymorphisms and Susceptibility to Breast Cancer Cancer Epidemiol. Biomarkers Prev., March 1, 2001; 10(3): 229 - 236. [Abstract] [Full Text]

				S.W. Baxter, D.Y.H. Choong, D.M. Eccles, and I.G. Campbell Polymorphic variation in CYP19 and the risk of breast cancer Carcinogenesis, February 1, 2001; 22(2): 347 - 349. [Abstract] [Full Text] [PDF]

				S.W. Baxter, E.J. Thomas, and I.G. Campbell GSTM1 null polymorphism and susceptibility to endometriosis and ovarian cancer Carcinogenesis, January 1, 2001; 22(1): 63 - 66. [Abstract] [Full Text] [PDF]

				A. B. Spurdle, P. M. Webb, D. M. Purdie, X. Chen, A. Green, and G. Chenevix-Trench Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype Carcinogenesis, January 1, 2001; 22(1): 67 - 72. [Abstract] [Full Text] [PDF]

				D. A. Lawlor, K. L. Beebe, R. Zaninelli, B. Trock, M. Cotterchio, and N. Kreiger RE: "ANTIDEPRESSANT MEDICATION USE AND BREAST CANCER RISK" Am. J. Epidemiol., December 1, 2000; 152(11): 1104 - 1016. [Full Text] [PDF]

				S. D. Stellman, M. V. Djordjevic, J. A. Britton, J. E. Muscat, M. L. Citron, M. Kemeny, E. Busch, and L. Gong Breast Cancer Risk in Relation to Adipose Concentrations of Organochlorine Pesticides and Polychlorinated Biphenyls in Long Island, New York Cancer Epidemiol. Biomarkers Prev., November 1, 2000; 9(11): 1241 - 1249. [Abstract] [Full Text]

				R. Goth-Goldstein, M. R. Stampfer, C. A. Erdmann, and M. Russell Interindividual variation in CYP1A1 expression in breast tissue and the role of genetic polymorphism Carcinogenesis, November 1, 2000; 21(11): 2119 - 2122. [Abstract] [Full Text] [PDF]

				A. B. Spurdle, J. L. Hopper, G. S. Dite, X. Chen, J. Cui, M. R. E. McCredie, G. G. Giles, M. C. Southey, D. J. Venter, D. F. Easton, et al. CYP17 Promoter Polymorphism and Breast Cancer in Australian Women Under Age Forty Years J Natl Cancer Inst, October 18, 2000; 92(20): 1674 - 1681. [Abstract] [Full Text] [PDF]

				A. C. Deitz, W. Zheng, M. A. Leff, M. Gross, W.-Q. Wen, M. A. Doll, G. H. Xiao, A. R. Folsom, and D. W. Hein N-Acetyltransferase-2 Genetic Polymorphism, Well-done Meat Intake, and Breast Cancer Risk among Postmenopausal Women Cancer Epidemiol. Biomarkers Prev., September 1, 2000; 9(9): 905 - 910. [Abstract] [Full Text]

				J. A. Williams and D. H. Phillips Mammary Expression of Xenobiotic Metabolizing Enzymes and Their Potential Role in Breast Cancer Cancer Res., September 1, 2000; 60(17): 4667 - 4677. [Abstract] [Full Text]

				P. A. Thompson and C. Ambrosone Chapter 7: Molecular Epidemiology of Genetic Polymorphisms in Estrogen Metabolizing Enzymes in Human Breast Cancer J Natl Cancer Inst Monographs, July 1, 2000; 2000(27): 125 - 134. [Abstract] [Full Text] [PDF]

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