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[Cancer Research 61, 3321-3325, April 15, 2001]
© 2001 American Association for Cancer Research

Epidemiology and Prevention

An Intronic Poly (AT) Polymorphism of the DNA Repair Gene XPC and Risk of Squamous Cell Carcinoma of the Head and Neck

A Case-Control Study1

Hongbing Shen, Erich M. Sturgis, Sikandar G. Khan, Yawei Qiao, Tala Shahlavi, Susan A. Eicher, Yiaochu Xu, Xinru Wang, Sara S. Strom, Margaret R. Spitz, Kenneth H. Kraemer and Qingyi Wei2

Departments of Epidemiology [H. S., E. M. S., Y. Q., S. S. S., M. R. S., Q. W.] and Head and Neck Surgery [E. M. S., S. A. E.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Department of Epidemiology and Statistics [H. S., Y. X., X. W.], School of Public Health, Nanjing Medical University, Nanjing, 210029 The People’s Republic of China; and Basic Research Laboratory [S. G. K., T. S., K. H. K.], National Cancer Institute, Bethesda, Maryland 20892


   ABSTRACT
Top
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity and genetic susceptibility to cancer. In a hospital-based case-control study of 287 non-Hispanic white patients with newly diagnosed SCCHN and 311 control subjects matched on age, sex, ethnicity, and smoking status, we investigated the role of a newly identified variant allele of XPC, XPC-PAT+. We found that the frequency of the XPC-PAT+ allele was higher in the cases (0.409) than in the controls (0.333; P = 0.007). Fifty cases (17.4%) and 37 controls (11.9%) were XPC-PAT+/+, and 135 (47.0%) cases and 133 controls (42.8%) were XPC-PAT+/-. XPC-PAT+/- and XPC-PAT+/+ subjects were at significantly increased risk for SCCHN [adjusted odds ratios = 1.44 and 1.85, respectively (95% confidence intervals, 1.01–2.05 and 1.12–3.05, respectively; trend test, P = 0.007)]. We did not find ethnic difference in the frequency of XPC-PAT+ allele among four groups aged between 19 and 75 years: non-Hispanic whites, 294; African-Americans, 178; Hispanic-Americans, 103; and native Chinese, 119 (0.333, 0.281, 0.296, and 0.353, respectively). The case-control findings support the hypothesis that the XPC-PAT+ allele may contribute to the risk of developing SCCHN.


   INTRODUCTION
Top
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Only a fraction of exposed individuals develops cancer, suggesting that there may be differences in individual susceptibility to cancer and possible gene-environment interactions. Both endogenous and exogenous exposures to carcinogens or genotoxic agents cause cell-cycle delays (1) that allow cells to repair DNA damage, and DRC3 is central to maintaining normal cellular functions (2) . Polymorphisms in DNA repair genes may contribute to variation in DRC in the general population (3 , 4) . Therefore, we hypothesized that inherited polymorphisms of DNA repair genes may contribute to genetic susceptibility to cancer.

We reported previously that patients with SCCHN have lower DRC than do normal control subjects (5) . We noted that these patients were more likely than healthy control subjects to exhibit genetic variants of two DNA repair genes, XRCC1 (6) and XPD (7) . Recently, a new intronic, biallelic poly (AT) insertion/deletion polymorphism (XPC-PAT) of the DNA repair gene XPC was reported (8) . XPC-PAT is in XPC intron 9 and is in linkage disequilibrium with a single-nucleotide polymorphism in XPC exon 15 that causes an amino acid change (Lys939 -> Gln) that does not alter XPC function in vitro (8) . However, the biological effects of these two new polymorphisms are not known. XPC protein binds to HR23B to form the XPC-HR23B complex, which is specifically involved in NER, probably as an early damage detector that plays a role in initiating NER (9) .

In this report, we used a modified PCR-based assay to rapidly genotype XPC-PAT (8) in a hospital-based, case-control study to test the hypothesis that the XPC-PAT polymorphism is associated with the risk of developing SCCHN. We also assessed ethnic differences in the frequency of the polymorphism in apparently healthy individuals of four ethnic groups: non-Hispanic whites, African-Americans, Hispanic-Americans, and native Chinese.


   MATERIALS AND METHODS
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects.
From May 1995 through December 1999, patients with histopathologically confirmed SCCHN (untreated primary tumors of the oral cavity, oropharynx, hypopharynx, and larynx) were recruited in the Department of Head and Neck Surgery of The University of Texas M. D. Anderson Cancer Center. Patients with primary tumors of the nasopharynx or sinonasal tract, primary tumors outside the upper aerodigestive tract, cervical metastases of unknown primary origin, or histopathological diagnoses of cancer other than squamous cell carcinoma were excluded. Because few patients were of other ethnic groups, only non-Hispanic white patients were included in this report. The non-Hispanic white healthy controls for these cases were recruited from enrollees in a managed care organization (10) and were frequency matched to the cases for age (±5 years), sex, and smoking status (never, former, or current). Blood samples were obtained from each subject after completion of personal interviews, and DNA was extracted and stored.

In addition, genomic DNA was obtained from 178 African-Americans, 103 Hispanic-Americans, and 119 healthy native Chinese donors, who did not have cancer, for evaluation of ethnic differences. These African-American and Hispanic-American subjects were blood donors and participants in cancer screening programs at M. D. Anderson; the Chinese subjects were control subjects in a population-based, case-control study conducted in Huai-an and Jin-tan counties, in central Jiangsu province, the People’s Republic of China, as described in detail elsewhere (11) . This research protocol was approved by the Institutional Review Boards of M. D. Anderson Cancer Center and of Nanjing Medical University.

PCR-based Genotyping and Sequencing.
PCR assays were used to amplify intron 9 of XPC, which contains an 83-bp poly (AT) insertion with a 5-bp deletion of GTAAC at position 1457–1461 (GenBank Accession No. AF076952) as previously described (8) . The primers (8) for XPC intron 9 generate a 266-bp fragment (the wild-type or PAT- allele) and a 344-bp fragment (the variant or PAT+ allele; Fig. 1ACitation ).



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  		Fig. 1. A, PCR products of XPC-PAT alleles. PCR generated two fragments: a 344-bp XPC-PAT+ fragment (L) and a 266-bp XPC-PAT- fragment (S). B, sequence of the wild-type PAT- allele; C, the sequence of variant PAT+ allele, showing the insertion of 83 As and Ts and deletion of five bases.

 
We used a modified PCR-based, nonradioactive assay for rapid genotyping of the XPC intronic poly (AT) polymorphism (Fig. 1A)Citation . To verify the allele sequence, the two fragments were further purified for PCR-directed sequencing to confirm the XPC intronic poly (AT) polymorphism. As shown in Fig. 1, B and CCitation , the variant XPC-PAT+ allele had an insertion of 83 bases consisting of only As and Ts and a deletion of GTAAC compared with the wild-type XPC-PAT- allele. One hundred seventy-seven samples from the African-American subjects were analyzed both at M. D. Anderson and at the National Cancer Institute. There was 100% agreement between both laboratories on genotype assignment. These results confirmed the initial report (8) and validated the modified PCR-based genotyping assay.

Statistical Analysis.
Univariate analysis was first performed to compare the distributions of age and sex and the frequencies of alleles and genotypes in each ethnic group. {chi}2 tests were used to compare the frequency distribution of the XPC-PAT+/+, XPC-PAT+/-, and XPC-PAT-/- genotypes with that expected from the Hardy-Weinberg model. Multivariate logistic regression analysis with adjustment for age, sex, smoking status, and alcohol use was performed to calculate OR, and 95% CIs. All statistical analyses were performed with Statistical Analysis System software (Version 6; SAS Institute Inc., Cary, NC).


   RESULTS
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
As shown in Table 1Citation , there was no difference in the distributions of age, sex, and smoking status between the cases and the controls, suggesting that the matching was adequate. There were more current alcohol users among the cases than among the controls, and the difference was statistically significant (P = 0.036; Table 1Citation ). The frequency of the variant XPC-PAT allele was higher in the cases (0.409) than in the controls (0.333), and the difference was of significance (P = 0.007; Table 1Citation ). The frequencies of both the heterozygous XPC-PAT+/- and homozygous XPC-PAT+/+ genotypes were statistically significantly higher in the cases (0.470 and 0.174, respectively) than in the controls (0.428 and 0.119, respectively; P = 0.026; Table 1Citation ). The heterozygous XPC-PAT+/- and homozygous XPC-PAT+/+ genotypes were associated with significantly increased risk for SCCHN (adjusted ORs, 1.44 and 1.85, respectively, and 95% CIs,1.01–2.05 and1.12–3.05, respectively), and the trend of the risk associated with the number of the XPC-PAT+ alleles was also statistically significant (P = 0.007) after adjustment for age, sex, smoking status, and alcohol use (Table 2)Citation .


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  		Table 1 Frequency distribution of selected demographic and risk factors in SCCHN patients and healthy controls in a non-Hispanic white population

 

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  		Table 2 Analysis of XPC genotype frequencies, ORs, and 95% CIs for SCCHN stratified by select variables

 
We next performed stratified analysis and assessed the trend for measuring risk associated with the number of the variant XPC-PAT+ alleles. In older subjects (>=66 years), the adjusted ORs were 2.11 and 5.55 for heterozygous and homozygous variants, respectively. The comparable adjusted ORs were 1.57 and 2.02 for men, respectively. A borderline increased risk was also found in former smokers and former alcohol users (Table 2)Citation . When stratified by tumor site, the variant XPC-PAT+ allele was associated with significantly increased risk for both oral and pharyngeal cancer (Table 2)Citation but with nonsignificantly increased risk for laryngeal cancer, perhaps because of the small number of cases in that histological type.

Ethnic differences in the frequencies of the XPC-PAT+ allele and XPC-PAT+/+ genotype were examined in the four ethnic groups of subjects of a similar age range (19–75 years) to avoid an age effect. As a result, 17 non-Hispanic white subjects > 75 years were excluded from the control group used in the case-control study described above. The distributions of age and sex for these four ethnic groups are presented in Table 3Citation . There were relatively more older (>=66 years) non-Hispanic whites and native Chinese than African-Americans and Hispanic-Americans, and there were fewer female subjects among native Chinese than among the other ethnic groups. However, the distributions of the three XPC-PAT genotypes did not statistically differ from those expected by Hardy-Weinberg equilibrium (Table 3)Citation . As shown in Table 3Citation , the frequencies of the variant XPC-PAT+ allele were 0.333, 0.281, 0.296, and 0.353 for non-Hispanic whites, African-Americans, Hispanic-Americans, and native Chinese, respectively. Although the frequencies of the XPC-PAT+/+ genotype were similar (in the range of 0.09–0.12) among the four groups, the frequencies of the XPC-PAT+/- genotype were nonsignificantly higher in non-Hispanic whites and native Chinese (0.43 and 0.47, respectively) than in African-Americans and Hispanic-Americans (0.39 and 0.35, respectively).


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  		Table 3 XPC-PAT polymorphism in healthy subjects of four ethnic groups

 

   DISCUSSION
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Compared with the general population, XP patients have a more than 1000-fold increased risk of developing sunlight-induced skin cancer as a result of defective NER (12) . To date, mutations that cause severe defects in NER have been identified in at least seven complementation genes (including XPC) for XP (13) . Moreover, individuals with a mild NER-deficient phenotype without XP are also at high risk of developing sunlight-induced skin cancers (4) . NER proteins not only repair UV light-induced photoproducts but also remove DNA adducts induced by tobacco carcinogens such as benzo[a]pyrene diol epoxide (14) . Therefore, polymorphisms in NER genes may affect the DNA repair phenotype, which contributes to risk of developing cancers of the skin (4) , the lung (15 , 16) , and the head and neck (5) . Variants of several DNA repair genes have only recently been described (3) and have sparked considerable research interest.

In this report, we found that the newly identified XPC-PAT+ polymorphism was significantly associated with increased risk for SCCHN in non-Hispanic whites, suggesting that this polymorphism may contribute to the etiology of SCCHN. The dose-response relationship between risk and the number of variant XPC-PAT+ alleles further strengthens the biological plausibility of the finding. The three subgroups of individuals who were at the highest risk associated with this XPC-PAT+ allele were as follows: older subjects, male subjects, and those who had only light exposure to smoking and alcohol. However, the findings about these subgroups are preliminary because of the relatively small number of subjects in each stratum and possibly as a result of multiple tests.

We also described the distribution and frequencies of the newly reported XPC-PAT+ allele and genotype in four ethnic groups: non-Hispanic whites, African-Americans, Hispanic-Americans, and native Chinese. Although ethnic differences in XP, a recessive disease characterized by defective DNA repair (13) , is remarkable and the frequency of XP is greater in Japanese than in Americans (12) , few reports have described ethnic differences in DNA repair gene polymorphisms in the general population. Recently, we reported a difference in the allele frequencies of the XRCC1 26304 T (in exons 5–6) and XRCC1 28152 A (in exon 10) allele in 166 healthy Chinese (0.346 and 0.256, respectively; Ref. 11 ) compared with 381 healthy non-Hispanic whites in one study (0.072 and 0.341, respectively; Ref. 6 ) and 169 healthy non-Hispanic whites in another study (0.06 and 0.37, respectively; Ref. 17 ). In the study reported here, we did not find significant differences in the frequencies of the XPC-PAT alleles among non-Hispanic whites, African-Americans, Hispanic-Americans, and native Chinese.

Studies of several essential genes support the importance of intronic polymorphisms in cancer susceptibility. Healey and coworkers (18) reported a nonsignificantly increased risk (OR, 1.56) of breast cancer associated with TTTA repeats in intron 4 of CYP19. This risk was nearly 2.5-fold in another Norwegian study (19) . Rothberg et al. (20) reported that a 799-bp deletion polymorphism attributable to Alu-Alu recombination in intron 2 of the retinoblastoma gene is associated with a more than eightfold increased risk of glioma. Single nucleotide polymorphisms in intron 12 of hHSH2 (21) are associated with increased risk for colorectal cancer. Unlike mutations in exons, these intronic mutations do not usually result in aberrant expression of the genes. However, their impact on cancer risk may be attributable to linkage with another susceptibility gene (21) or to induction of aberrant splicing of mRNA, leading to mutant mRNAs (22) . Although the effect of the XPC-PAT intronic polymorphism on NER is not known, it is in linkage disequilibrium with another single nucleotide polymorphism in the XPC exon 15, which causes an amino acid change from Lys to Gln that does not alter the function of the XPC gene in an in vitro assay (8) .

Nucleotide structure analysis suggested that the 83-bp XPC insertion is adjacent to a portion of a retrotransposon (23) : a 0.7-kb inverse complement of a truncated portion of the 3' end of a long interspersed nuclear element of class L1MB3. Retrotransposons may play a role in exon shuffling (24) or abnormal splicing (25, 26, 27) and have been shown to be active in the human genome (23) . Therefore, it is possible that this polymorphism alters gene functions that remain to be identified. The knowledge acquired from the mutated XPC gene suggests that a normal XPC gene is critical for the cells to complete excision repair of bulky DNA lesions (28) , including smoking-induced DNA adducts.

In conclusion, we found that the new XPC-PAT+ polymorphism contributed to the risk of SCCHN. It is possible that our findings, particularly from the stratified analysis, are attributable to chance because of the relatively small numbers in the subgroups. Furthermore, the functional relevance of this XPC intronic polymorphism and its role in cancer susceptibility remain to be determined in larger epidemiological studies. As new technologies are developed for easier genotyping of many (perhaps hundreds) of genes at once, it will become possible to construct genetic profiles of risk and to develop risk models incorporating combinations of many polymorphisms in many genes, each of which contributes only slightly to the overall risk. The type of descriptive work presented here will be critical to deciding which genetic polymorphisms to include in future risk-assessment studies and statistical modeling.


   ACKNOWLEDGMENTS
 
We thank Dr. Maureen Goode for her scientific editing, Min Fu for her technical support, Margaret Lung for her recruitment of the subjects, and Joanne Sider and Joyce Brown for manuscript preparation.


   FOOTNOTES
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported in part by the NIH Grants CA55769 and CA86390 (to M. R. S.); CA70334, CA74851, and CA70242 (to Q. W.); and CA16672 to the M. D. Anderson Cancer Center; by National Institute of Environmental Health Sciences Grant ES07784 (to J. D.); by funds collected pursuant to the Comprehensive Tobacco Settlement of 1998 and appropriated by the 76th Legislature to the M. D. Anderson Cancer Center; and by Natural Science Foundation of Jiangsu Province Grant 98015 (to Y. X.), China. Back

2 To whom requests for reprints should be addressed, at Department of Epidemiology, Box 189, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792-3020; Fax: (713) 792-0807; E-mail: qwei{at}mail.mdanderson.org Back

3 The abbreviations used are: DRC, DNA repair capacity; SCCHN, squamous cell carcinoma of the head and neck; OR, odds ratio; CI, confidence interval; XP, xeroderma pigmentosum; NER, nucleotide excision repair. Back

Received 11/ 3/00. Accepted 2/13/01.


   REFERENCES
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Hartwell L. H., Weinert T. A. Checkpoints: controls that assure the order of cell cycle events. Science (Wash DC), 246: 629-633, 1989.[Abstract/Free Full Text]
  2. Sancar A. DNA repair in human. Annu. Rev. Genet., 29: 69-105, 1995.[Medline]
  3. Shen M. R., Jones I. M., Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res., 58: 604-608, 1998.[Abstract/Free Full Text]
  4. Wei Q., Matanoski G. M., Farmer E. R., Hedayati M., Grossman L. DNA repair and aging in basal cell carcinoma: a molecular epidemiology study. Proc. Natl. Acad. Sci. USA, 90: 1614-1618, 1993.[Abstract/Free Full Text]
  5. Cheng L., Eicher S. A., Guo Z., Hong W. K., Spitz M. R., Wei Q. Reduced DNA repair capacity in head and neck cancer patients. Cancer Epidemiol. Biomark. Prev., 7: 465-468, 1998.[Abstract/Free Full Text]
  6. Sturgis E. M., Castillo E. J., Li L., Zheng R., Eicher S. A., Clayman G. L., Strom S. S., Spitz M. R., Wei Q. Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck: a case-control analysis. Carcinogenesis (Lond.), 20: 2125-2129, 1999.[Abstract/Free Full Text]
  7. Sturgis E. M., Zheng R., Li L., Castillo E. J., Eicher S. A., Chen M., Strom S. S., Spitz M. R., Wei Q. XPD/ERCC2 polymorphisms and risk for the head and neck cancer: a case-control analysis. Carcinogenesis (Lond.), 21: 2219-2223, 2000.[Abstract/Free Full Text]
  8. Khan S. G., Metter E. J., Tarone R. E., Bohr V. A., Grossman L., Hedayati M., Bale S. J., Emmert S., Kraemer K. H. A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism. Carcinogenesis (Lond.), 21: 1821-1825, 2000.[Abstract/Free Full Text]
  9. Sugasawa K., Ng J. M., Masutani C., Iwai S., van der Spek P. J., Eker A. P., Hanaoka F., Bootsma D., Hoeijmakers J. H. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol. Cell, 2: 223-232, 1998.[Medline]
  10. Hudmon K. S., Honn S. E., Jiang H., Chamberlain R. M., Xiang W., Ferry G., Gosbee W., Spitz M. R. Identifying and recruiting healthy control subjects from a managed care organization: a methodology for molecular epidemiologic case-control studies of cancer. Cancer Epidemiol. Biomark. Prev., 6: 565-571, 1997.[Abstract]
  11. Shen H. B., Xu Y. C., Qian Y., Yu R. B., Qin Y., Zhou L., Wang X. R., Spitz M. R., Wei Q. Polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese population. Int. J. Cancer, 88: 601-606, 2000.[Medline]
  12. Kraemer K. H., Lee M. M., Andrews A. D., Lambert W. C. The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. Arch. Dermatol., 130: 1018-1021, 1994.[Abstract/Free Full Text]
  13. Bootsma D., Kraemer K. H., Cleaver J. E., Hoeijmakers J. H. J. Nucleotide exicision repair syndromes: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy Vogelstein B. Kinzler K. W. eds. . The Genetic Basis of Human Cancer, : 245-274, McGraw-Hill New York 1998.
  14. Denissenko M. F., Pao A., Tang M., Pfeifer G. P. Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in p53. Science (Wash DC), 274: 430-432, 1996.[Abstract/Free Full Text]
  15. Wei Q., Cheng L., Hong W. K., Spitz M. R. Reduced DNA repair capacity in lung cancer patients. Cancer Res., 56: 4103-4107, 1996.[Abstract/Free Full Text]
  16. Cheng L., Spitz M. R., Hong W. K., Wei Q. Reduced expression levels of nucleotide excision repair genes in lung cancer: a case-control analysis. Carcinogenesis (Lond.), 21: 1527-1530, 2000.[Abstract/Free Full Text]
  17. Lunn R. M., Langlois R. G., Hsieh L. L., Thompson C. L., Bell D. A. XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res., 59: 2557-2561, 1999.[Abstract/Free Full Text]
  18. Healey C. S., Dunning A. M., Durocher F., Teare D., Pharoah P. D., Luben R. N., Easton D. F., Ponder B. A. Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk. Carcinogenesis (Lond.), 21: 189-193, 2000.[Abstract/Free Full Text]
  19. Kristensen V. N., Andersen T. I., Lindblom A., Erikstein B., Magnus P., Borresen-Dale A. L. A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics, 8: 43-48, 1998.[Medline]
  20. Rothberg P. G., Ponnuru S., Baker D., Bradley J. F., Freeman A. I., Cibis G. W., Harris D. J., Heruth D. P. A deletion polymorphism due to Alu-Alu recombination in intron 2 of the retinoblastoma gene: association with human gliomas. Mol. Carcinog., 19: 69-73, 1997.[Medline]
  21. Goessl C., Plaschke J., Pistorius S., Hahn M., Frank S., Hampl M., Gorgens H., Koch R., Saeger H. D., Schackert H. K. An intronic germline transition in the HNPCC gene hMSH2 is associated with sporadic colorectal cancer. Eur. J. Cancer, 33: 1869-1874, 1997.
  22. Sugimoto K., Toyoshima H., Sakai R., Miyagawa K., Hagiwara K., Ishikawa F., Takaku F., Yazaki Y., Hirai H. Frequent mutations in the p53 gene in human myeloid leukemia cell lines. Blood, 79: 2378-2383, 1992.[Abstract/Free Full Text]
  23. Kazazian H. H. J., Moran J. V. The impact of L1 retrotransposons on the human genome. Nat. Genet., 19: 19-24, 1998.[Medline]
  24. Moran J. V., DeBerardinis R. J., Kazazian H. H. J. Exon shuffling by L1 retrotransposition. Science (Wash DC), 283: 1530-1534, 1999.[Abstract/Free Full Text]
  25. Narita N., Nishio H., Kitoh Y., Ishikawa Y., Minami R., Nakamura H., Matsuo M. Insertion of a 5' truncated L1 element into the 3' end of exon 44 of the dystrophin gene resulted in skipping of the exon during splicing in a case of Duchenne muscular dystrophy. J. Clin. Investig., 91: 1862-1867, 1993.
  26. Mulhardt C., Fischer M., Gass P., Simon-Chazottes D., Guenet J. L., Kuhse J., Betz H., Becker C. M. The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron, 13: 1003-1015, 1994.[Medline]
  27. Takahara T., Ohsumi T., Kuromitsu J., Shibata K., Sasaki N., Okazaki Y., Shibata H., Sato S., Yoshiki A., Kusakabe M., Muramatsu M., Ueki M., Okuda K., Hayashizaki Y. Dysfunction of the Orleans reeler gene arising from exon skipping due to transposition of a full-length copy of an active L1 sequence into the skipped exon. Hum. Mol. Genet., 5: 989-993, 1996.[Abstract/Free Full Text]
  28. Li L., Bales E. S., Peterson C. A., Legerski R. J. Characterization of molecular defects in xeroderma pigmentosum group C. Nat. Genet., 5: 413-417, 1993.[Medline]



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XPA, haplotypes, and risk of basal and squamous cell carcinoma
Carcinogenesis, August 1, 2006; 27(8): 1670 - 1675.
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 Cancer Epidemiol. Biomarkers Prev.Home page
W.-Y. Huang, S. I. Berndt, D. Kang, N. Chatterjee, S. J. Chanock, M. Yeager, R. Welch, R. S. Bresalier, J. L. Weissfeld, and R. B. Hayes
Nucleotide Excision Repair Gene Polymorphisms and Risk of Advanced Colorectal Adenoma: XPC Polymorphisms Modify Smoking-Related Risk.
Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 306 - 311.
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 CarcinogenesisHome page
S. G. Khan, K.-S. Oh, T. Shahlavi, T. Ueda, D. B. Busch, H. Inui, S. Emmert, K. Imoto, V. Muniz-Medina, C. C. Baker, et al.
Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients
Carcinogenesis, January 1, 2006; 27(1): 84 - 94.
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 Cancer Epidemiol. Biomarkers Prev.Home page
J. M. Weiss, N. S. Weiss, C. M. Ulrich, J. A. Doherty, L. F. Voigt, and C. Chen
Interindividual Variation in Nucleotide Excision Repair Genes and Risk of Endometrial Cancer
Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2524 - 2530.
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 Proc. Natl. Acad. Sci. USAHome page
M. C. Hollander, R. T. Philburn, A. D. Patterson, S. Velasco-Miguel, E. C. Friedberg, R. I. Linnoila, and A. J. Fornace Jr.
Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis
PNAS, September 13, 2005; 102(37): 13200 - 13205.
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 CarcinogenesisHome page
A. G. Casson, Z. Zheng, S. C. Evans, P. J. Veugelers, G. A. Porter, and D. L. Guernsey
Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma
Carcinogenesis, September 1, 2005; 26(9): 1536 - 1541.
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 CarcinogenesisHome page
S. Blankenburg, I. R. Konig, R. Moessner, P. Laspe, K.-M. Thoms, U. Krueger, S. G. Khan, G. Westphal, C. Berking, M. Volkenandt, et al.
Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case-control study
Carcinogenesis, June 1, 2005; 26(6): 1085 - 1090.
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 CarcinogenesisHome page
S. Pavanello, A. Pulliero, E. Siwinska, D. Mielzynska, and E. Clonfero
Reduced nucleotide excision repair and GSTM1-null genotypes influence anti-B[a]PDE-DNA adduct levels in mononuclear white blood cells of highly PAH-exposed coke oven workers
Carcinogenesis, January 1, 2005; 26(1): 169 - 175.
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 Cancer Epidemiol. Biomarkers Prev.Home page
M. S. Marin, M. F. Lopez-Cima, L. Garcia-Castro, T. Pascual, M. G. Marron, and A. Tardon
Poly (AT) Polymorphism in Intron 11 of the XPC DNA Repair Gene Enhances the Risk of Lung Cancer
Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1788 - 1793.
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 CarcinogenesisHome page
S. Sanyal, F. Festa, S. Sakano, Z. Zhang, G. Steineck, U. Norming, H. Wijkstrom, P. Larsson, R. Kumar, and K. Hemminki
Polymorphisms in DNA repair and metabolic genes in bladder cancer
Carcinogenesis, May 1, 2004; 25(5): 729 - 734.
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 Cancer Res.Home page
L. Hagmar, U. Stromberg, S. Bonassi, I.-L. Hansteen, L. E. Knudsen, C. Lindholm, and H. Norppa
Impact of Types of Lymphocyte Chromosomal Aberrations on Human Cancer Risk: Results from Nordic and Italian Cohorts
Cancer Res., March 15, 2004; 64(6): 2258 - 2263.
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 Cancer Res.Home page
T.-L. Tseng, Y.-P. Shih, Y.-C. Huang, C.-K. Wang, P.-H. Chen, J.-G. Chang, K.-T. Yeh, Y.-M. A. Chen, and K. H. Buetow
Genotypic and Phenotypic Characterization of a Putative Tumor Susceptibility Gene, GNMT, in Liver Cancer
Cancer Res., February 1, 2003; 63(3): 647 - 654.
[Abstract] [Full Text] [PDF]

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E. L. Goode, C. M. Ulrich, and J. D. Potter
Polymorphisms in DNA Repair Genes and Associations with Cancer Risk
Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1513 - 1530.
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 Nucleic Acids ResHome page
S. G. Khan, V. Muniz-Medina, T. Shahlavi, C. C. Baker, H. Inui, T. Ueda, S. Emmert, T. D. Schneider, and K. H. Kraemer
The human XPC DNA repair gene: arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function
Nucleic Acids Res., August 15, 2002; 30(16): 3624 - 3631.
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 CarcinogenesisHome page
Y. Qiao, M. R. Spitz, H. Shen, Z. Guo, S. Shete, M. Hedayati, L. Grossman, H. Mohrenweiser, and Q. Wei
Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes
Carcinogenesis, February 1, 2002; 23(2): 295 - 299.
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