Role of Polymorphisms in Cancer Susceptibility

Abstract

Genetic variations or polymorphisms existing in the human genome can confer genetic susceptibility to cancer. Rare early onset cancer predisposition syndromes such as Li‐Fraumeni and Cowden syndromes typically involve germline mutations exhibiting high‐penetrance effects, but these account for only a small proportion of human cancers. For sporadic cancers, early monogenic association studies focusing on candidate genes with strong biological hypothesis have demonstrated an increased risk of cancers associated with polymorphisms in genes involved in cell cycle control, carcinogen metabolism, DNA (deoxyribonucleic acid) repair, apoptosis, inflammation and epigenetic regulation. Recent genome‐wide association studies have gone beyond the monogenic candidate gene approach to search across the entire genome for cancer susceptibility loci. This exponential knowledge has increased our understanding of carcinogenesis and provided translational research opportunities into personalised risk assessment, therapy and drug discovery.

Key Concepts:

  • Rare hereditary cancer syndromes such as Li‐Fraumeni syndrome typically involve high‐penetrance mutations of oncogenes or tumour suppressor genes, but account for a minority of human cancers.

  • The overwhelming majority of cancer susceptibility in the normal population is likely attributable to common genetic variations or polymorphisms in the human genome.

  • Candidate gene approaches have identified several polymorphisms of known oncogenes and tumour suppressor genes, as well as genes involved in carcinogen metabolism, DNA repair and cell‐cycle control that are associated with cancer susceptibility.

  • The increased risk conferred by each polymorphism is small.

  • Data from separate association studies are often conflicting. Meta‐analysis can be used to integrate conflicting findings across several studies.

  • The functional mechanisms by which many polymorphisms lead to cancer susceptibility has not been established.

  • In recent years, high‐resolution public databases of genetic information, technological advances and reduced costs of genotyping have led to a rapid emergence of genome‐wide association studies (GWAS) that survey the entire genome for cancer susceptibility loci.

  • By these approaches, putative risk loci, novel cancer genes have increased biological insights into carcinogenesis.

  • This exponential increase in knowledge has opened new horizons to understand oncogenesis and translational research opportunities into personalised risk assessment, therapy and drug discovery.

Keywords: polymorphisms; cancer susceptibility; single nucleotide polymorphisms; genome‐wide association studies; hereditary cancer syndromes

References

Abdel‐Rahman SZ, Salama SA, Au WW et al. (2000) Role of polymorphic CYP2E1 and CYP2D6 genes in NNK‐induced chromosome aberrations in cultured human lymphocytes. Pharmacogenetics 10(3): 239–249.

Amtha R, Ching CS, Zain R et al. (2009) GSTM1, GSTT1 and CYP1A1 polymorphisms and risk of oral cancer: a case‐control study in Jakarta, Indonesia. Asian Pacific Journal of Cancer Prevention 10(1): 21–26.

Bai J, Dai J, Yu H et al. (2009) Cigarette smoking, MDM2 SNP309, gene‐environment interactions, and lung cancer risk: a meta‐analysis. Journal of Toxicology and Environmental Health Part A 72(11–12): 677–682.

Berndt SI, Platz EA, Fallin MD et al. (2006) Genetic variation in the nucleotide excision repair pathway and colorectal cancer risk. Cancer Epidemiology, Biomarkers and Prevention 15(11): 2263–2269.

Blankenburg S, Konig IR, Moessner R et al. (2005) Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case‐control study. Carcinogenesis 26(6): 1085–1090.

Boccia S, Hung R, Ricciardi G et al. (2008) Meta‐ and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: a huge‐GSEC review. American Journal of Epidemiology 167(5): 505–516.

Bond GL, Hu W, Bond EE et al. (2004) A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 119(5): 591–602.

Cabral RE, Caldeira‐de‐Araujo A, Cabral‐Neto JB et al. (2010) Analysis of GSTM1 and GSTT1 polymorphisms in circulating plasma DNA of lung cancer patients. Molecular and Cellular Biochemistry 338(1–2): 263–269.

Candeias MM, Malbert‐Colas L, Powell DJ et al. (2008) P53 mRNA controls p53 activity by managing Mdm2 functions. Nature Cell Biology 10(9): 1098–1105.

Chang BL, Cramer SD, Wiklund F et al. (2009) Fine mapping association study and functional analysis implicate a SNP in MSMB at 10q11 as a causal variant for prostate cancer risk. Human Molecular Genetics 18(7): 1368–1375.

Chao C, Zhang ZF, Berthiller J et al. (2006) NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta‐analysis. Cancer Epidemiology, Biomarkers and Prevention 15(5): 979–987.

Chen K, Jiang QT and He HQ (2005) Relationship between metabolic enzyme polymorphism and colorectal cancer. World Journal of Gastroenterology 11(3): 331–335.

Chua HW, Ng D, Choo S et al. (2010) Effect of MDM2 SNP309 and p53 codon 72 polymorphisms on lung cancer risk and survival among non‐smoking Chinese women in Singapore. BMC Cancer 10: 88.

Chung CC, Magalhaes WC, Gonzalez‐Bosquet J et al. (2010) Genome‐wide association studies in cancer: current and future directions. Carcinogenesis 31(1): 111–120.

Crowther‐Swanepoel D, Broderick P, Di Bernardo MC et al. (2010) Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nature Genetics 42(2): 132–136.

Das P, Shaik AP and Bammidi VK (2009) Meta‐analysis study of glutathione‐S‐transferases (GSTM1, GSTP1, and GSTT1) gene polymorphisms and risk of acute myeloid leukemia. Leukemia and Lymphoma 50(8): 1345–1351.

Delort L, Satih S, Kwiatkowski F et al. (2010) Evaluation of breast cancer risk in a multigenic model including low penetrance genes involved in xenobiotic and estrogen metabolisms. Nutrition and Cancer 62(2): 243–251.

Demircan B, Dyer LM, Gerace M et al. (2009) Comparative epigenomics of human and mouse mammary tumors. Genes Chromosomes Cancer 48(1): 83–97.

Ding D, Xu L, Menon M et al. (2004) Effect of a short CAG (glutamine) repeat on human androgen receptor function. Prostate 58(1): 23–32.

Ding JH, Li SP, Cao HX et al. (2009) Genetic polymorphisms of alcohol dehydrogenase‐2 and aldehyde dehydrogenase‐2 associated with the susceptibility on esophageal cancer. Zhonghua Liu Xing Bing Xue Za Zhi 30(5): 455–458.

Do TN, Ucisik‐Akkaya E, Davis CF et al. (2009) TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility. Cancer Genetics and Cytogenetics 195(1): 31–36.

Dong LM, Potter JD, White E et al. (2008) Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. Journal of the American Medical Association 299(20): 2423–2436.

Duncan TJ, Al‐Attar A, Rolland P et al. (2010) Cytoplasmic p27 expression is an independent prognostic factor in ovarian cancer. International Journal of Gynecological Pathology 29(1): 8–18.

Dunning AM, Healey CS, Pharoah PD et al. (1999) A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiology, Biomarkers and Prevention 8(10): 843–854.

Easton DF, Pooley KA, Dunning AM et al. (2007) Genome‐wide association study identifies novel breast cancer susceptibility loci. Nature 447(7148): 1087–1093.

Economopoulos KP and Sergentanis TN (2010) GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta‐analysis. European Journal of Cancer 46(9): 1617–1631.

El‐Omar EM (2006) Role of host genes in sporadic gastric cancer. Best Practice and Research Clinical Gastroenterology 20(4): 675–686.

Feng J, Sun X, Sun N et al. (2009) XPA A23G polymorphism is associated with the elevated response to platinum‐based chemotherapy in advanced non‐small cell lung cancer. Acta Biochimica et Biophysica Sinica (Shanghai) 41(5): 429–435.

Festa F, Kumar R, Sanyal S et al. (2005) Basal cell carcinoma and variants in genes coding for immune response, DNA repair, folate and iron metabolism. Mutation Research 574(1–2): 105–111.

Fontana L, Delort L, Joumard L et al. (2009) Genetic polymorphisms in CYP1A1, CYP1B1, COMT, GSTP1 and NAT2 genes and association with bladder cancer risk in a French cohort. Anticancer Research 29(5): 1631–1635.

Francisco G, Menezes PR, Eluf‐Neto J et al. (2008) XPC polymorphisms play a role in tissue‐specific carcinogenesis: a meta‐analysis. European Journal of Human Genetics 16(6): 724–734.

Gail MH (2009) Value of adding single‐nucleotide polymorphism genotypes to a breast cancer risk model. Journal of the National Cancer Institute 101(13): 959–963.

Gal TJ, Huang WY, Chen C et al. (2005) DNA repair gene polymorphisms and risk of second primary neoplasms and mortality in oral cancer patients. Laryngoscope 115(12): 2221–2231.

Garcia‐Closas M, Kristensen V, Langerod A et al. (2007a) Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer. International Journal of Cancer 121(11): 2532–2538.

Garcia‐Closas M, Malats N, Silverman D et al. (2005) NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta‐analyses. Lancet 366(9486): 649–659.

Garcia‐Closas M, Troester MA, Qi Y et al. (2007b) Common genetic variation in GATA‐binding protein 3 and differential susceptibility to breast cancer by estrogen receptor alpha tumor status. Cancer Epidemiology, Biomarkers and Prevention 16(11): 2269–2275.

Gemignani F, Moreno V, Landi S et al. (2004) A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA. Oncogene 23(10): 1954–1956.

Ghoussaini M, Song H, Koessler T et al. (2008) Multiple loci with different cancer specificities within the 8q24 gene desert. Journal of the National Cancer Institute 100(13): 962–966.

Glick AB (2004) TGFbeta1, back to the future: revisiting its role as a transforming growth factor. Cancer Biology and Therapy 3(3): 276–283.

Golka K, Hermes M, Selinski S et al. (2009) Susceptibility to urinary bladder cancer: relevance of rs9642880[T] GSTM1 0/0 and occupational exposure. Pharmacogenet Genomics (epub ahead of print).

Gonzalez‐Zuloeta Ladd AM, Arias‐Vasquez A, Siemes C et al. (2007) Transforming‐growth factor beta1 Leu10Pro polymorphism and breast cancer morbidity. European Journal of Cancer 43(2): 371–374.

Gorouhi F, Islami F, Bahrami H et al. (2008) Tumour‐necrosis factor‐A polymorphisms and gastric cancer risk: a meta‐analysis. British Journal of Cancer 98(8): 1443–1451.

Guey LT, Garcia‐Closas M, Murta‐Nascimento C et al. (2010) Genetic susceptibility to distinct bladder cancer subphenotypes. European Urology 57(2): 283–292.

Haghighi MM, Radpour R, Mahmoudi T et al. (2009) Association between MTHFR polymorphism (C677T) with nonfamilial colorectal cancer. Oncology Research 18(2–3): 57–63.

Hayes JD and Strange RC (1995) Potential contribution of the glutathione S‐transferase supergene family to resistance to oxidative stress. Free Radical Research 22(3): 193–207.

Hein DW (2002) Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mutation Research 506–507: 65–77.

Hellmig S, Bartscht T, Fischbach W et al. (2008) Interleukin‐10 (‐819 C/T) and TNF‐A (‐308 G/A) as risk factors for H. pylori‐associated gastric MALT‐lymphoma. Digestive Diseases and Sciences 53(7): 2007–2008.

Hrstka R, Coates PJ, and Vojtesek B (2009) Polymorphisms in p53 and the p53 pathway: roles in cancer susceptibility and response to treatment. Journal of Cellular and Molecular Medicine 13(3): 440–453.

Hu Z, Wei Q, Wang X et al. (2004) DNA repair gene XPD polymorphism and lung cancer risk: a meta‐analysis. Lung Cancer 46(1): 1–10.

Huang CC, Chien WP, Wong RH et al. (2007a) NAT2 fast acetylator genotype is associated with an increased risk of colorectal cancer in Taiwan. Diseases of the Colon and Rectum 50(7): 981–989.

Huang WY, Olshan AF, Schwartz SM et al. (2005) Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer: a pooled analysis. Cancer Epidemiology, Biomarkers and Prevention 14(7): 1747–1753.

Huang Y, Han S, Li Y et al. (2007b) Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta‐analysis. Journal of Human Genetics 52(1): 73–85.

IHGSC (2004) Finishing the euchromatic sequence of the human genome. Nature 431(7011): 931–945.

IHMP (2003) The international HapMap project. Nature 426(6968): 789–796.

Ioannidis JP, Ntzani EE, Trikalinos TA et al. (2001) Replication validity of genetic association studies. Nature Genetics 29(3): 306–309.

Ismail SI, Ababneh NA, Khader Y et al. (2009) Methylenetetrahydrofolate reductase genotype association with the risk of follicular lymphoma. Cancer Genetics and Cytogenetics 195(2): 120–124.

de Jong MM, Nolte IM, te Meerman GJ et al. (2002) Low‐penetrance genes and their involvement in colorectal cancer susceptibility. Cancer Epidemiology, Biomarkers and Prevention 11(11): 1332–1352.

Kiyohara C, Takayama K, and Nakanishi Y (2006) Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk: a meta‐analysis. Lung Cancer 54(3): 267–283.

Kuligina E, Reiner A, Imyanitov EN et al (2010) Evaluating cancer epidemiologic risk factors using multiple primary malignancies. Epidemiology 21(3): 366–372.

Kuo KT, Mao TL, Chen X et al. (2010) DNA copy numbers profiles in affinity‐purified ovarian clear cell carcinoma. Clinical Cancer Research 16(7): 1997–2008.

Lander ES, Linton LM, Birren B et al. (2001) Initial sequencing and analysis of the human genome. Nature 409(6822): 860–921.

Langevin SM, Lin D, Matsuo K et al. (2009) Review and pooled analysis of studies on MTHFR C677T polymorphism and esophageal cancer. Toxicology Letters 184(2): 73–80.

Li X, Dumont P, Della Pietra A et al. (2005) The codon 47 polymorphism in p53 is functionally significant. Journal of Biological Chemistry 280(25): 24245–24251.

Li H and Tai BC (2006) RNASEL gene polymorphisms and the risk of prostate cancer: a meta‐analysis. Clinical Cancer Research 12(19): 5713–5719.

Liang G, Xing D, Miao X et al. (2003) Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. International Journal of Cancer 105(5): 669–673.

Liao RY, Mao C, Qiu LX et al. (2009) TGFBR1*6A/9A polymorphism and cancer risk: a meta‐analysis of 13 662 cases and 14 147 controls. Molecular Biology Reports (epub ahead of print).

Liu G, Zhou W, Wang LI et al. (2004) MPO and SOD2 polymorphisms, gender, and the risk of non‐small cell lung carcinoma. Cancer Letters 214(1): 69–79.

Loh M, Koh KX, Yeo BH et al. (2009) Meta‐analysis of genetic polymorphisms and gastric cancer risk: variability in associations according to race. European Journal of Cancer 45(14): 2562–2568.

Lum SS, Chua HW, Li H et al. (2008) MDM2 SNP309 G allele increases risk but the T allele is associated with earlier onset age of sporadic breast cancers in the Chinese population. Carcinogenesis 29(4): 754–761.

Mahadeo KM, Dhall G, Panigrahy A et al. (2010) Subacute methotrexate neurotoxicity and cerebral venous sinus thrombosis in a 12‐year old with acute lymphoblastic leukemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: homocysteine‐mediated methotrexate neurotoxicity via direct endothelial injury. Pediatric Hematology and Oncology 27(1): 46–52.

Marin MS, Lopez‐Cima MF, Garcia‐Castro L et al. (2004) Poly (AT) polymorphism in intron 11 of the XPC DNA repair gene enhances the risk of lung cancer. Cancer Epidemiology, Biomarkers and Prevention 13(11 Pt 1): 1788–1793.

Mojtahedi Z, Haghshenas MR, Hosseini SV et al. (2010) p53 codon 72 polymorphism in stomach and colorectal adenocarcinomas in Iranian patients. Indian Journal of Cancer 47(1): 31–34.

Morris RD (1994) Meta‐analysis in cancer epidemiology. Environmental Health Perspectives 102(suppl. 8): 61–66.

Pabalan N, Bapat B, Sung L et al. (2008) Cyclin D1 Pro241Pro (CCND1‐G870A) polymorphism is associated with increased cancer risk in human populations: a meta‐analysis. Cancer Epidemiology, Biomarkers and Prevention 17(10): 2773–2781.

Papaemmanuil E, Hosking FJ, Vijayakrishnan J et al. (2009) Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nature Genetics 41(9): 1006–1010.

Persson C, Engstrand L, Nyren O et al. (2009) Interleukin 1‐beta gene polymorphisms and risk of gastric cancer in Sweden. Scandinavian Journal of Gastroenterology 44(3): 339–345.

Piao JM, Shin MH, Kweon SS et al. (2009) Glutathione‐S‐transferase (GSTM1, GSTT1) and the risk of gastrointestinal cancer in a Korean population. World Journal of Gastroenterology 15(45): 5716–5721.

Pim D and Banks L (2004) p53 polymorphic variants at codon 72 exert different effects on cell cycle progression. International Journal of Cancer 108(2): 196–199.

Probst‐Hensch NM, Steiner JH, Schraml P et al. (2010) IGFBP2 and IGFBP3 protein expressions in human breast cancer: association with hormonal factors and obesity. Clinical Cancer Research 16(3): 1025–1032.

Qiu LX, Li RT, Zhang JB et al. (2009) The E‐cadherin (CDH1)–160 C/A polymorphism and prostate cancer risk: a meta‐analysis. European Journal of Human Genetics 17(2): 244–249.

Rebbeck TR (1997) Molecular epidemiology of the human glutathione S‐transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiology, Biomarkers and Prevention 6(9): 733–743.

Rebbeck TR, Kantoff PW, Krithivas K et al. (1999) Modification of BRCA1‐associated breast cancer risk by the polymorphic androgen‐receptor CAG repeat. American Journal of Human Genetics 64(5): 1371–1377.

Ryk C, Kumar R, Sanyal S et al. (2006) Influence of polymorphism in DNA repair and defence genes on p53 mutations in bladder tumours. Cancer Letters 241(1): 142–149.

Sainger RN, Shah FD, Telang SD et al. (2009) Telomere attrition and telomerase activity are associated with GSTM1 polymorphism in oral cancer. Cancer Biomarkers 5(4): 189–195.

Schayek H, Bentov I, Sun S et al. (2010) Progression to metastatic stage in a cellular model of prostate cancer is associated with methylation of the androgen receptor gene and transcriptional suppression of the insulin‐like growth factor‐I receptor gene. Experimental Cell Research 316(9): 1479–1488.

Schmidt MK, Reincke S, Broeks A et al. (2007) Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium. Cancer Research 67(19): 9584–9590.

Sergentanis TN and Economopoulos KP (2009) Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta‐analysis. Breast Cancer Research and Treatment (epub ahead of print).

Setiawan VW, Schumacher FR, Haiman CA et al. (2007) CYP17 genetic variation and risk of breast and prostate cancer from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). Cancer Epidemiology, Biomarkers and Prevention 16(11): 2237–2246.

Shi X, Zhou S, Wang Z et al. (2008) CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta‐analysis. Lung Cancer 59(2): 155–163.

Shlien A and Malkin D (2010) Copy number variations and cancer susceptibility. Current Opinion in Oncology 22(1): 55–63.

Sigurdson AJ, Bhatti P, Doody MM et al. (2007) Polymorphisms in apoptosis‐ and proliferation‐related genes, ionizing radiation exposure, and risk of breast cancer among U.S. radiologic technologists. Cancer Epidemiology, Biomarkers and Prevention 16(10): 2000–2007.

Sillanpaa P, Heikinheimo L, Kataja V et al. (2007) CYP1A1 and CYP1B1 genetic polymorphisms, smoking and breast cancer risk in a Finnish Caucasian population. Breast Cancer Research and Treatment 104(3): 287–297.

Skibola CF, Bracci PM, Nieters A et al. (2010) Tumor necrosis factor (TNF) and lymphotoxin‐alpha (LTA) polymorphisms and risk of non‐Hodgkin lymphoma in the InterLymph Consortium. American Journal of Epidemiology 171(3): 267–276.

Sobti RC, Sharma S, Joshi A et al. (2004) Genetic polymorphism of the CYP1A1, CYP2E1, GSTM1 and GSTT1 genes and lung cancer susceptibility in a north indian population. Molecular and Cellular Biochemistry 266(1–2): 1–9.

Sotelo J, Esposito D, Duhagon MA et al. (2010) Long‐range enhancers on 8q24 regulate c‐Myc. Proceedings of the National Academy of Sciences of the USA 107(7): 3001–3005.

Steinmann K, Sandner A, Schagdarsurengin U et al. (2009) Frequent promoter hypermethylation of tumor‐related genes in head and neck squamous cell carcinoma. Oncology Reports 22(6): 1519–1526.

Sterpone S, Mastellone V, Padua L et al. (2010) Single‐nucleotide polymorphisms in BER and HRR genes, XRCC1 haplotypes and breast cancer risk in Caucasian women. Journal of Cancer Research and Clinical Oncology 136(4): 631–636.

Sun J, Turner A, Xu J et al. (2007) Genetic variability in inflammation pathways and prostate cancer risk. Urologic Oncology 25(3): 250–259.

Sun J, Wiklund F, Zheng SL et al. (2005) Sequence variants in Toll‐like receptor gene cluster (TLR6‐TLR1‐TLR10) and prostate cancer risk. Journal of the National Cancer Institute 97(7): 525–532.

Sun L, Sun YH, Wang B et al. (2008) Methylenetetrahydrofolate reductase polymorphisms and susceptibility to gastric cancer in Chinese populations: a meta‐analysis. European Journal of Cancer Prevention 17(5): 446–452.

Suneetha KJ, Nancy KN, Rajalekshmy KR et al. (2008) Role of GSTM1 (Present/Null) and GSTP1 (Ile105Val) polymorphisms in susceptibility to acute lymphoblastic leukemia among the South Indian population. Asian Pacific Journal of Cancer Prevention 9(4): 733–736.

Tijhuis MJ, Visker MH, Aarts JM et al. (2008) NQO1 and NFE2L2 polymorphisms, fruit and vegetable intake and smoking and the risk of colorectal adenomas in an endoscopy‐based population. International Journal of Cancer 122(8): 1842–1848.

Tse D, Zhai R, Zhou W et al. (2008) Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk. Cancer Causes Control 19(10): 1077–1083.

Vousden KH and Lane DP (2007) p53 in health and disease. Nature Reviews. Molecular Cell Biology 8(4): 275–283.

Wacholder S, Chanock S, Garcia‐Closas M et al. (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. Journal of the National Cancer Institute 96(6): 434–442.

Wang M, Gu D, Zhang Z et al. (2009) XPD polymorphisms, cigarette smoking, and bladder cancer risk: a meta‐analysis. Journal of Toxicology and Environmental Health Part A 72(11–12): 698–705.

Wei SZ, Zhan P, Shi MQ et al. (2010) Predictive value of ERCC1 and XPD polymorphism in patients with advanced non‐small cell lung cancer receiving platinum‐based chemotherapy: a systematic review and meta‐analysis. Medical Oncology (epub ahead of print).

Whibley C, Pharoah PD and Hollstein M (2009) p53 polymorphisms: cancer implications. Nature Reviews. Cancer 9(2): 95–107.

Wu MS, Shun CT, Huang SP et al. (2004) Effect of interleukin‐1beta and glutathione S‐transferase genotypes on the development of gastric mucosa‐associated lymphoid tissue lymphoma. Haematologica 89(8): 1015–1017.

Ye Z and Song H (2005) Glutathione S‐transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of acute leukaemia: a systematic review and meta‐analysis. European Journal of Cancer 41(7): 980–989.

Zhang D, Chen C, Fu X et al. (2008) A meta‐analysis of DNA repair gene XPC polymorphisms and cancer risk. Journal of Human Genetics 53(1): 18–33.

Zheng H, Wang Z, Shi X et al. (2009) XRCC1 polymorphisms and lung cancer risk in Chinese populations: a meta‐analysis. Lung Cancer 65(3): 268–273.

Zhu Y, Lai M, Yang H et al. (2007) Genotypes, haplotypes and diplotypes of XPC and risk of bladder cancer. Carcinogenesis 28(3): 698–703.

Zhuo WL, Zhang YS, Wang Y et al. (2009) Association studies of CYP1A1 and GSTM1 polymorphisms with esophageal cancer risk: evidence‐based meta‐analyses. Archives of Medical Research 40(3): 169–179.

Zintzaras E (2009) Glutathione S‐transferase M1 and T1 genes and susceptibility to chronic myeloid leukemia: a meta‐analysis. Genetic Testing and Molecular Biomarkers 13(6): 791–797.

Further Reading

Robson ME, Storm CD, Weitzel J and Wollins DS, Offit K (2010) American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. Journal of Clinical Oncology 28(5): 893–901.

Shastry BS (2009) SNPs: impact on gene function and phenotype. Methods in Molecular Biology 578: 3–22.

Smith JG and Newton‐Cheh C (2009) Genome‐wide association study in humans. Methods in Molecular Biology 573: 231–258.

Spitz MR and Bondy ML (2010) The evolving discipline of molecular epidemiology of cancer. Carcinogenesis 31(1): 127–134.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Tan, Iain Beehuat, Ngeow, Joanne, and Tan, Patrick(Sep 2010) Role of Polymorphisms in Cancer Susceptibility. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022403]