Review of studies on metabolic genes and cancer in populations of African descent

Department of Epidemiology, State University of New York Downstate Medical Center, New York, NY 11203, USA.
Genetics in medicine: official journal of the American College of Medical Genetics (Impact Factor: 7.33). 12/2009; 12(1):12-8. DOI: 10.1097/GIM.0b013e3181c8e160
Source: PubMed


Genetic polymorphisms described for a number of enzymes involved in the metabolism of tobacco carcinogens and alcohol have been linked to increase cancer risk. Racial disparities in cancer between whites and populations of African descent are well documented. In addition to differences in access to health care, both environment and genetic factors and their interaction may contribute to the increased cancer risk in minority populations. We reviewed the literature to identify case-control studies that included subjects of African descent. Meta-analyses investigating the association of genetic polymorphisms in tobacco metabolic genes and cancer were performed. Although several genes and cancers have been studied, only one or two studies per gene for each cancer site have been published, with the exception of breast (CYP1A1 and CYP1B1), lung (GSTM1, CYP1A1, and NQO1), and prostate (CYP3A4 A293G and CYP17). Marginal statistically significant associations were observed for CYP3A4 A293G and CYP17 5'UTR polymorphisms and prostate cancer. Our findings support the need for additional genetic association studies of breast, prostate, and lung cancers that include a larger number of minority participants. Because incidence and mortality rates for these cancers rank highest among populations of African descent, concentrated research in these areas are warranted.

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Available from: Camille C Ragin
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    • "Most of the agents occur as part of our diet. Chemoprotective agents regulate the expression of drug-metabolizing enzymes because their activity may contribute to the sensitivity of different individuals to develop cancer (Moon et al. 2006; Ragin et al. 2010). Confirming the effects of CAPE on a specific CYP will help us elucidate the mechanism of CAPE as a chemoprotective agent in the modified resistant hepatocyte model of hepatocarcinogenesis, which may become a referent model (Bai et al. 2011; Beltran-Ramirez et al. 2008; Beltran-Ramirez et al. 2010; Carrasco-Legleu et al. 2006). "
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    ABSTRACT: Studies of cancer chemoprevention with caffeic acid phenethyl ester (CAPE) in the resistant hepatocyte model of hepatocarcinogenesis have shown the participation of CYP drug metabolizing enzymes. To prevent neoplastic and preneoplasic lesions, we must specifically identify which CYP activities are modified in the mechanism of action of CAPE. Male Fischer-344 rats were pretreated with CAPE twelve hours before administration of diethylnitrosamine (DEN) and were sacrificed twelve hours after CAPE and twelve hours, twenty-four hours, twenty-four days, and twelve months after DEN. Other rats were treated with the CYP inhibitors α-naphthoflavone or SKF525A and sacrificed twenty-four hours and twenty-four days after DEN. Microsomes were obtained from livers to quantify protein using Western blot. Diethylnitrosamine metabolism was measured based on nitrite formation and liver histology using GGT histochemistry. Caffeic acid phenethyl ester diminished the protein levels of CYP1A2 and CYP2B1/2. The inhibition of CYP2B1/2 prevented the appearance of preneoplastic lesions. Microsomal assays demonstrated that CAPE interfered with DEN activation diminishing nitrites similar to SKF525A and probably mediated by CYP2B1/2 inhibition. A single dose of CAPE before DEN treatment reduced the appearance of tumors by 43%. These results confirmed that CAPE is a promising agent to confer chemoprotection in liver cancer and should be considered for human therapies.
    Full-text · Article · Jan 2012 · Toxicologic Pathology
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    • "Moreover, alcohol consumption is an important risk factor for numerous cancers worldwide [7]. Due to hereditary differences/genetic polymorphisms [8]–[9], the incidence and causes of cancers and the responses to anti-cancer drugs vary substantially among different ethnic groups. Numerous researchers have studied the association between alcohol consumption and cancers in Chinese people [10]–[17]. "
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    ABSTRACT: Alcohol consumption is increasing worldwide and is associated with numerous cancers. This systematic review examined the role of alcohol in the incidence of cancer in the Chinese population. Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Cohort and case-control studies on the effect of alcohol use on cancers in Chinese were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were independently abstracted by two reviewers. Odds ratios (OR) or relative risks (RR) were pooled using RevMan 5.0. Heterogeneity was evaluated using the Q test and I-squared statistic. P<.01 was considered statistically significant. Pooled results from cohort studies indicated that alcohol consumption was not associated with gastric cancer, esophageal cancers (EC) or lung cancer. Meta-analysis of case-control studies showed that alcohol consumption was a significant risk factor for five cancers; the pooled ORs were 1.79 (99% CI, 1.47-2.17) EC, 1.40 (99% CI, 1.19-1.64) gastric cancer, 1.56 (99% CI, 1.16-2.09) hepatocellular carcinoma, 1.21 (99% CI, 1.00-1.46) nasopharyngeal cancer and 1.71 (99% CI, 1.20-2.44) oral cancer. Pooled ORs of the case-control studies showed that alcohol consumption was protective for female breast cancer and gallbladder cancer: OR 0.76 (99% CI, 0.60-0.97) and 0.70 (99% CI, 0.49-1.00) respectively. There was no significant correlation between alcohol consumption and lung cancer, colorectal cancer, pancreatic cancer, cancer of the ampulla of Vater, prostate cancer or extrahepatic cholangiocarcinoma. Combined results of case-control and cohort studies showed that alcohol consumption was associated with 1.78- and 1.40-fold higher risks of EC and gastric cancer but was not significantly associated with lung cancer. Health programs focused on limiting alcohol intake may be important for cancer control in China. Further studies are needed to examine the interaction between alcohol consumption and other risk factors for cancers in Chinese and other populations.
    Full-text · Article · Apr 2011 · PLoS ONE
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    • "Surprisingly, in our meta-analysis, just one study by Shen et al.(Shen et al., 2001) reported genetic polymorphisms by race (non-Hispanic Whites, African-Americans, Hispanic- Americans, and native Chinese) without finding significant ethnic differences among the four groups. We have also observed a lack of publications concerning African-Americans or individuals of African descent while evaluating other gene polymorphisms(Ragin et al., 2010). Future assessments of genetic polymorphisms in the DNA repair pathway in minority populations are needed. "
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    ABSTRACT: Polymorphisms in DNA repair genes have been reported contributing factors in head and neck cancer risk but studies have shown conflicting results. To clarify the impact of DNA repair gene polymorphisms in head and neck cancer risk. A meta-analysis including 30 case-control studies was performed. Marginally statistically significant association was found for XRCC1 codon 399 (for Caucasians only), XPD Asp312Asn and XRCC1 codon 194 variants and head and neck cancer. Assessments of the effects of smoking, alcohol, human papillomavirus and race/ethnicity on the association between DNA repair gene polymorphisms and head and neck cancer are needed.
    Full-text · Article · Aug 2010 · Biomarkers
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