MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk
O6-methylguanine DNA methyl-transferase (MGMT) is the only known critical gene involved in cellular defense against alkylating agents in the DNA direct reversal repair (DRR) pathway. Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified...
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| creator | Shen, Jing Terry, Mary Beth Gammon, Marilie D. Gaudet, Mia M. Teitelbaum, Susan L. Eng, Sybil M. Sagiv, Sharon K. Neugut, Alfred I. Santella, Regina M. |
| description | O6-methylguanine DNA methyl-transferase (MGMT) is the only known critical gene involved in cellular defense against alkylating agents in the DNA direct reversal repair (DRR) pathway. Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified [C250T (Leu84Phe), A427G (Ile143Val) and A533G (Lys178Arg)]. To examine the importance of the DRR pathway in risk for breast cancer and the potential interaction with cigarette smoking and dietary antioxidants, we genotyped for these variants using biospecimens from the Long Island Breast Cancer Study Project. Genotyping was performed by a high throughput assay with fluorescence polarization and included 1067 cases and 1110 controls. Overall, there was no main effect between any variant genotype, haplotype or diplotype and breast cancer risk. Heavy smoking (>31 pack-year) significantly increased breast cancer risk for women with the codon 84 variant T-allele [odds ratio, OR = 3.0, 95% confidence interval (95% CI) = 1.4–6.2]. An inverse association between fruits and vegetables consumption and breast cancer risk was observed among women with the wild-type genotype for codon 84 (OR = 0.8, 95% CI = 0.6–0.9 for ≥35 servings of fruits and vegetables per week and CC genotype versus those with |
| doi_str_mv | 10.1093/carcin/bgi179 |
| format | Article |
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Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified [C250T (Leu84Phe), A427G (Ile143Val) and A533G (Lys178Arg)]. To examine the importance of the DRR pathway in risk for breast cancer and the potential interaction with cigarette smoking and dietary antioxidants, we genotyped for these variants using biospecimens from the Long Island Breast Cancer Study Project. Genotyping was performed by a high throughput assay with fluorescence polarization and included 1067 cases and 1110 controls. Overall, there was no main effect between any variant genotype, haplotype or diplotype and breast cancer risk. Heavy smoking (>31 pack-year) significantly increased breast cancer risk for women with the codon 84 variant T-allele [odds ratio, OR = 3.0, 95% confidence interval (95% CI) = 1.4–6.2]. An inverse association between fruits and vegetables consumption and breast cancer risk was observed among women with the wild-type genotype for codon 84 (OR = 0.8, 95% CI = 0.6–0.9 for ≥35 servings of fruits and vegetables per week and CC genotype versus those with <35 servings per week and CC genotype). The association between fruits and vegetables consumption and reduced breast cancer risk was apparent among women with at least one variant allele for codon 143 (OR = 0.6, 95% CI = 0.5–0.9 for ≥35 servings of fruits and vegetables per week and AG or GG genotype versus those with <35 servings per week and AA genotype). Similar patterns were observed for dietary α-carotene and supplemental β-carotene, but not for supplemental vitamins C and E. These data suggest that polymorphisms in MGMT may modulate the inverse association previously observed between fruits and vegetables consumption, dietary antioxidants and breast cancer risk, and support the importance of fruits and vegetables on breast cancer risk reduction.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgi179</identifier><identifier>PMID: 16014702</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Aged ; Alkylating agents ; Antioxidants - metabolism ; Biological and medical sciences ; Breast Neoplasms - epidemiology ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Carcinogenesis, carcinogens and anticarcinogens ; Case-Control Studies ; confidence interval ; Diet ; Dietary Supplements ; direct reversal repair ; DRR ; Female ; Fluorescence ; Fruit ; Genotype ; Gynecology. Andrology. Obstetrics ; Haplotypes - genetics ; Humans ; ICR ; interaction contrast ratio ; LIBCSP ; Long Island Breast Cancer Study Project ; Mammary gland diseases ; Medical sciences ; Menopause ; MGMT ; Middle Aged ; New York - epidemiology ; O-Methylguanine-DNA Methyltransferase - genetics ; O6-methylguanine DNA methyl-transferase ; odds ratio ; Polymorphism, Single Nucleotide ; Risk Factors ; Smoking ; Tobacco, tobacco smoking ; Toxicology ; Tumors ; Vegetables</subject><ispartof>Carcinogenesis (New York), 2005-12, Vol.26 (12), p.2131-2137</ispartof><rights>2006 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Dec 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-f5652a65ae49d00622a3d13a4ae4949ff8972b5dc97b423db9fcedc0e208cfeb3</citedby><cites>FETCH-LOGICAL-c489t-f5652a65ae49d00622a3d13a4ae4949ff8972b5dc97b423db9fcedc0e208cfeb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17300721$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16014702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shen, Jing</creatorcontrib><creatorcontrib>Terry, Mary Beth</creatorcontrib><creatorcontrib>Gammon, Marilie D.</creatorcontrib><creatorcontrib>Gaudet, Mia M.</creatorcontrib><creatorcontrib>Teitelbaum, Susan L.</creatorcontrib><creatorcontrib>Eng, Sybil M.</creatorcontrib><creatorcontrib>Sagiv, Sharon K.</creatorcontrib><creatorcontrib>Neugut, Alfred I.</creatorcontrib><creatorcontrib>Santella, Regina M.</creatorcontrib><title>MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>O6-methylguanine DNA methyl-transferase (MGMT) is the only known critical gene involved in cellular defense against alkylating agents in the DNA direct reversal repair (DRR) pathway. Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified [C250T (Leu84Phe), A427G (Ile143Val) and A533G (Lys178Arg)]. To examine the importance of the DRR pathway in risk for breast cancer and the potential interaction with cigarette smoking and dietary antioxidants, we genotyped for these variants using biospecimens from the Long Island Breast Cancer Study Project. Genotyping was performed by a high throughput assay with fluorescence polarization and included 1067 cases and 1110 controls. Overall, there was no main effect between any variant genotype, haplotype or diplotype and breast cancer risk. Heavy smoking (>31 pack-year) significantly increased breast cancer risk for women with the codon 84 variant T-allele [odds ratio, OR = 3.0, 95% confidence interval (95% CI) = 1.4–6.2]. An inverse association between fruits and vegetables consumption and breast cancer risk was observed among women with the wild-type genotype for codon 84 (OR = 0.8, 95% CI = 0.6–0.9 for ≥35 servings of fruits and vegetables per week and CC genotype versus those with <35 servings per week and CC genotype). The association between fruits and vegetables consumption and reduced breast cancer risk was apparent among women with at least one variant allele for codon 143 (OR = 0.6, 95% CI = 0.5–0.9 for ≥35 servings of fruits and vegetables per week and AG or GG genotype versus those with <35 servings per week and AA genotype). Similar patterns were observed for dietary α-carotene and supplemental β-carotene, but not for supplemental vitamins C and E. These data suggest that polymorphisms in MGMT may modulate the inverse association previously observed between fruits and vegetables consumption, dietary antioxidants and breast cancer risk, and support the importance of fruits and vegetables on breast cancer risk reduction.</description><subject>Adult</subject><subject>Aged</subject><subject>Alkylating agents</subject><subject>Antioxidants - metabolism</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - epidemiology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Case-Control Studies</subject><subject>confidence interval</subject><subject>Diet</subject><subject>Dietary Supplements</subject><subject>direct reversal repair</subject><subject>DRR</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Fruit</subject><subject>Genotype</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Haplotypes - genetics</subject><subject>Humans</subject><subject>ICR</subject><subject>interaction contrast ratio</subject><subject>LIBCSP</subject><subject>Long Island Breast Cancer Study Project</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Menopause</subject><subject>MGMT</subject><subject>Middle Aged</subject><subject>New York - epidemiology</subject><subject>O-Methylguanine-DNA Methyltransferase - genetics</subject><subject>O6-methylguanine DNA methyl-transferase</subject><subject>odds ratio</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><subject>Smoking</subject><subject>Tobacco, tobacco smoking</subject><subject>Toxicology</subject><subject>Tumors</subject><subject>Vegetables</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90c9rFDEUB_Agit2uHr1KECweHJtfM5kcpeiu0CJKheIlZJI3a7ozk22Swfa_N2UXFzx4eiTvwwt5X4ReUfKBEsXPrYnWT-fdxlOpnqAFFQ2pGG3JU7QgVPCKcy5O0GlKt4TQhtfqOTqhTWlJwhYoXK2urvEGppAfdoDH4ObBZEg4_wJsUgrWm-zDlHAH-TfAhK3fmAg5A05j2Ppp8x47D9nEB2ymQu-9KzWVg8NdBJMytmayEHH0afsCPevNkODloS7Rj8-fri_W1eXX1ZeLj5eVFa3KVV83NTNNbUAoR0jDmOGOciMeL4Tq-1ZJ1tXOKtkJxl2negvOEmCktT10fInO9nN3MdzNkLIefbIwDGaCMCdNFW9lK-sC3_0fCsUaUnNCC33zD70Nc5zKNzQr8wSXJZAlqvbIxpBShF7voh_LdjQl-jExvU9M7xMr_vVh6NyN4I76EFEBbw_AJGuGPpZl-nR0khMiGT0-7FOG-799E7e6kVzWen3zU3-j39erG9Xqlv8BPTmw5Q</recordid><startdate>20051201</startdate><enddate>20051201</enddate><creator>Shen, Jing</creator><creator>Terry, Mary Beth</creator><creator>Gammon, Marilie D.</creator><creator>Gaudet, Mia M.</creator><creator>Teitelbaum, Susan L.</creator><creator>Eng, Sybil M.</creator><creator>Sagiv, Sharon K.</creator><creator>Neugut, Alfred I.</creator><creator>Santella, Regina M.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20051201</creationdate><title>MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk</title><author>Shen, Jing ; Terry, Mary Beth ; Gammon, Marilie D. ; Gaudet, Mia M. ; Teitelbaum, Susan L. ; Eng, Sybil M. ; Sagiv, Sharon K. ; Neugut, Alfred I. ; Santella, Regina M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-f5652a65ae49d00622a3d13a4ae4949ff8972b5dc97b423db9fcedc0e208cfeb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Alkylating agents</topic><topic>Antioxidants - metabolism</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - epidemiology</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Case-Control Studies</topic><topic>confidence interval</topic><topic>Diet</topic><topic>Dietary Supplements</topic><topic>direct reversal repair</topic><topic>DRR</topic><topic>Female</topic><topic>Fluorescence</topic><topic>Fruit</topic><topic>Genotype</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>ICR</topic><topic>interaction contrast ratio</topic><topic>LIBCSP</topic><topic>Long Island Breast Cancer Study Project</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Menopause</topic><topic>MGMT</topic><topic>Middle Aged</topic><topic>New York - epidemiology</topic><topic>O-Methylguanine-DNA Methyltransferase - genetics</topic><topic>O6-methylguanine DNA methyl-transferase</topic><topic>odds ratio</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Factors</topic><topic>Smoking</topic><topic>Tobacco, tobacco smoking</topic><topic>Toxicology</topic><topic>Tumors</topic><topic>Vegetables</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shen, Jing</creatorcontrib><creatorcontrib>Terry, Mary Beth</creatorcontrib><creatorcontrib>Gammon, Marilie D.</creatorcontrib><creatorcontrib>Gaudet, Mia M.</creatorcontrib><creatorcontrib>Teitelbaum, Susan L.</creatorcontrib><creatorcontrib>Eng, Sybil M.</creatorcontrib><creatorcontrib>Sagiv, Sharon K.</creatorcontrib><creatorcontrib>Neugut, Alfred I.</creatorcontrib><creatorcontrib>Santella, Regina M.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shen, Jing</au><au>Terry, Mary Beth</au><au>Gammon, Marilie D.</au><au>Gaudet, Mia M.</au><au>Teitelbaum, Susan L.</au><au>Eng, Sybil M.</au><au>Sagiv, Sharon K.</au><au>Neugut, Alfred I.</au><au>Santella, Regina M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>26</volume><issue>12</issue><spage>2131</spage><epage>2137</epage><pages>2131-2137</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>O6-methylguanine DNA methyl-transferase (MGMT) is the only known critical gene involved in cellular defense against alkylating agents in the DNA direct reversal repair (DRR) pathway. Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified [C250T (Leu84Phe), A427G (Ile143Val) and A533G (Lys178Arg)]. To examine the importance of the DRR pathway in risk for breast cancer and the potential interaction with cigarette smoking and dietary antioxidants, we genotyped for these variants using biospecimens from the Long Island Breast Cancer Study Project. Genotyping was performed by a high throughput assay with fluorescence polarization and included 1067 cases and 1110 controls. Overall, there was no main effect between any variant genotype, haplotype or diplotype and breast cancer risk. Heavy smoking (>31 pack-year) significantly increased breast cancer risk for women with the codon 84 variant T-allele [odds ratio, OR = 3.0, 95% confidence interval (95% CI) = 1.4–6.2]. An inverse association between fruits and vegetables consumption and breast cancer risk was observed among women with the wild-type genotype for codon 84 (OR = 0.8, 95% CI = 0.6–0.9 for ≥35 servings of fruits and vegetables per week and CC genotype versus those with <35 servings per week and CC genotype). The association between fruits and vegetables consumption and reduced breast cancer risk was apparent among women with at least one variant allele for codon 143 (OR = 0.6, 95% CI = 0.5–0.9 for ≥35 servings of fruits and vegetables per week and AG or GG genotype versus those with <35 servings per week and AA genotype). Similar patterns were observed for dietary α-carotene and supplemental β-carotene, but not for supplemental vitamins C and E. These data suggest that polymorphisms in MGMT may modulate the inverse association previously observed between fruits and vegetables consumption, dietary antioxidants and breast cancer risk, and support the importance of fruits and vegetables on breast cancer risk reduction.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>16014702</pmid><doi>10.1093/carcin/bgi179</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Alkylating agents Antioxidants - metabolism Biological and medical sciences Breast Neoplasms - epidemiology Breast Neoplasms - genetics Breast Neoplasms - metabolism Carcinogenesis, carcinogens and anticarcinogens Case-Control Studies confidence interval Diet Dietary Supplements direct reversal repair DRR Female Fluorescence Fruit Genotype Gynecology. Andrology. Obstetrics Haplotypes - genetics Humans ICR interaction contrast ratio LIBCSP Long Island Breast Cancer Study Project Mammary gland diseases Medical sciences Menopause MGMT Middle Aged New York - epidemiology O-Methylguanine-DNA Methyltransferase - genetics O6-methylguanine DNA methyl-transferase odds ratio Polymorphism, Single Nucleotide Risk Factors Smoking Tobacco, tobacco smoking Toxicology Tumors Vegetables |
| title | MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk |
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