TY - JOUR
T1 - Nucleotide excision repair gene polymorphisms, meat intake and colon cancer risk
AU - Steck, Susan E.
AU - Butler, Lesley M.
AU - Keku, Temitope
AU - Antwi, Samuel
AU - Galanko, Joseph
AU - Sandler, Robert S.
AU - Hu, Jennifer J.
N1 - Funding Information:
This research was supported in part by grants from the National Institutes of Health ( P30 DK34987 , R01CA66635 , R01CA090898 , and K07CA102640 ), an American Society of Preventive Oncology Cancer Prevention Research Fellowship (SES), and the National Institute of Child Health and Human Development ’s Building Interdisciplinary Research Careers in Women's Health (BIRCWH) grant 5K12HD051958 (LMB).
PY - 2014/4
Y1 - 2014/4
N2 - Purpose: Much of the DNA damage from colon cancer-related carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH) from red meat cooked at high temperature, are repaired by the nucleotide excision repair (NER) pathway. Thus, we examined whether NER non-synonymous single nucleotide polymorphisms (nsSNPs) modified the association between red meat intake and colon cancer risk. Methods: The study consists of 244 African-American and 311 white colon cancer cases and population-based controls (331 African Americans and 544 whites) recruited from 33 counties in North Carolina from 1996 to 2000. Information collected by food frequency questionnaire on meat intake and preparation methods were used to estimate HCA and benzo(a)pyrene (BaP, a PAH) intake. We tested 7 nsSNPs in 5 NER genes: XPC A499V and K939Q, XPD D312N and K751Q, XPF R415Q, XPG D1104H, and RAD23B A249V. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. Results: Among African Americans, we observed a statistically significant positive association between colon cancer risk and XPC 499 AV+VV genotype (OR=1.7, 95% CI: 1.1, 2.7, AA as referent), and an inverse association with XPC 939 QQ (OR=0.3, 95%CI: 0.2, 0.8, KK as referent). These associations were not observed among whites. For both races combined, there was interaction between the XPC 939 genotype, well-done red meat intake and colon cancer risk (OR=1.5, 95% CI=1.0, 2.2 for high well-done red meat and KK genotype as compared to low well-done red meat and KK genotype, pinteraction=0.05). Conclusions: Our data suggest that NER nsSNPs are associated with colon cancer risk and may modify the association between well-done red meat intake and colon cancer risk.
AB - Purpose: Much of the DNA damage from colon cancer-related carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH) from red meat cooked at high temperature, are repaired by the nucleotide excision repair (NER) pathway. Thus, we examined whether NER non-synonymous single nucleotide polymorphisms (nsSNPs) modified the association between red meat intake and colon cancer risk. Methods: The study consists of 244 African-American and 311 white colon cancer cases and population-based controls (331 African Americans and 544 whites) recruited from 33 counties in North Carolina from 1996 to 2000. Information collected by food frequency questionnaire on meat intake and preparation methods were used to estimate HCA and benzo(a)pyrene (BaP, a PAH) intake. We tested 7 nsSNPs in 5 NER genes: XPC A499V and K939Q, XPD D312N and K751Q, XPF R415Q, XPG D1104H, and RAD23B A249V. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. Results: Among African Americans, we observed a statistically significant positive association between colon cancer risk and XPC 499 AV+VV genotype (OR=1.7, 95% CI: 1.1, 2.7, AA as referent), and an inverse association with XPC 939 QQ (OR=0.3, 95%CI: 0.2, 0.8, KK as referent). These associations were not observed among whites. For both races combined, there was interaction between the XPC 939 genotype, well-done red meat intake and colon cancer risk (OR=1.5, 95% CI=1.0, 2.2 for high well-done red meat and KK genotype as compared to low well-done red meat and KK genotype, pinteraction=0.05). Conclusions: Our data suggest that NER nsSNPs are associated with colon cancer risk and may modify the association between well-done red meat intake and colon cancer risk.
KW - Case-control study
KW - Colon cancer
KW - DNA repair
KW - Diet
KW - Meat
KW - Polymorphism
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U2 - 10.1016/j.mrfmmm.2014.02.004
DO - 10.1016/j.mrfmmm.2014.02.004
M3 - Article
C2 - 24607854
AN - SCOPUS:84897406060
SN - 0027-5107
VL - 762
SP - 24
EP - 31
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1
ER -