Genetic polymorphism of cholesterol 7α‐hydroxylase (CYP7A1) and colorectal adenomas: Self Defense Forces Health Study

Tabata, Shinji; Yin, Guang; Ogawa, Shinsaku; Yamaguchi, Keizo; Mineshita, Masamichi; Kono, Suminori

doi:10.1111/j.1349-7006.2006.00182.x

Cited by 18 publications

(12 citation statements)

References 37 publications

(37 reference statements)

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“…, adenoma characteristics, age, and sex). Our results corroborate the findings of Tabata et al , (28) and Hagiwara et al , (27) who reported an association between the CYP7A1 promoter variant and risk of CRA and CRC, respectively. Collectively, these results strengthen the link between genetic variation in CYP7A1 and CRC risk and provide additional support favoring the role of bile acid metabolism in the biology of colorectal carcinogenesis.…”

Section: Discussionsupporting

confidence: 93%

“…Further, the uniqueness of the sample set, which includes only polyp formers, limits the generalizability of our results. Despite these limitations, the overall findings show consistency with biological mechanisms ( CYP7A1 variation as a determinant of bile acid levels and CYP7A1 gene regulation as a putative UDCA target) and, more importantly, replicate prior associations between genetic variation in CYP7A1 and risk of CRA development (27, 28). …”

Section: Discussionsupporting

confidence: 63%

“…In contrast, no variant-related differences were detected in healthy controls. In case-control studies, carriage of the -204CC genotype was associated with reduced risk of both CRC and CRA arising in the proximal colon, suggesting a protective gene effect resulting from reduced bile acid synthesis in CC carriers (27, 28). More recently, a genome-wide association study (GWAS) has provided confirmatory evidence linking allelic variation in CYP7A1 to total cholesterol and LDL (29), with findings from an independent study showing that such variation modifies individual response to the lipid-lowering effects of atorvastatin (30).…”

Section: Introductionmentioning

confidence: 99%

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Risk Modification of Colorectal Adenoma byCYP7A1Polymorphisms and the Role of Bile Acid Metabolism in Carcinogenesis

Wertheim

Smith

Fang

et al. 2012

Cancer Prevention Research

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Cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, is a postulated gene modifier of colorectal cancer risk and target for the therapeutic bile acid, ursodeoxycholic acid (UDCA). We investigated associations between CYP7A1 polymorphisms and fecal bile acids, colorectal adenoma (CRA), and UDCA efficacy for CRA prevention. Seven tagging, single-nucleotide polymorphisms (SNPs) in CYP7A1 were measured in 703 (355 UDCA, 348 placebo) participants of a phase III chemoprevention trial, of which 495 had known baseline fecal bile acid concentrations. In the placebo arm, participants with two minor Grs8192871 alleles (tag for a low-activity promoter polymorphism at -204) had lower odds of high secondary bile acids (OR, 0.26; 95% CI, 0.10–0.69), and CRA at 3 years' follow-up (OR, 0.41; 95% CI, 0.19–0.89), than AA carriers. Haplotype construction from the six polymorphic SNPs showed participants with the third-most common haplotype (Crs10957057Crs8192879Grs8192877Trs11786580Ars8192871Grs13251096) had higher odds of high primary bile acids (OR, 2.34; 95% CI, 1.12–4.89) and CRA (OR, 1.89; 95% CI, 1.00–3.57) than those with the most common CTACAG haplotype. Furthermore, three SNPs (rs8192877, rs8192871, and rs13251096) each modified UDCA efficacy for CRA prevention, and CCGTAG-haplotype carriers experienced 71% lower odds of CRA recurrence with UDCA treatment, an effect not present for other haplotypes (test for UDCA-by-haplotype interaction, P=0.020). Our findings support CYP7A1 polymorphisms as determinants of fecal bile acids and risk factors for CRA. Further, UDCA efficacy for CRA prevention may be modified by genetic variation in CYP7A1, limiting treatment benefit to a subgroup of the population.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Risk Modification of Colorectal Adenoma byCYP7A1Polymorphisms and the Role of Bile Acid Metabolism in Carcinogenesis

Wertheim

Smith

Fang

et al. 2012

Cancer Prevention Research

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“…Cholecystectomy, which changes the profile of bile acids, has been generally associated with risk of proximal colon cancer, 40 and polymorphisms in the cholesterol 7α-hydroxylase (CYP7A1), the rate limiting enzyme producing bile acids from cholesterol, have been associated with risk of proximal colon cancer and adenoma. 41,42 Although not entirely consistently observed, in some studies associations with hyperinsulinemia or the metabolic syndrome have been observed only for proximal colon cancer or adenoma, 43,44 or the associations were stronger in the proximal colon. 45,46 Future studies of obesity and weight change should examine potential subsite differences.…”

Section: Discussionmentioning

confidence: 98%

Prospective weight change and colon cancer risk in male US health professionals

Thygesen

Grønbæk

Johansen

et al. 2008

Intl Journal of Cancer

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Epidemiological studies are remarkably consistent, especially among men, in showing that overweight and obesity [body mass index (BMI) >25] are associated with increased risk of colon cancer. However, no prospective studies address the influence of weight change in adulthood on subsequent colon cancer risk. In this study, we investigated whether weight change influences colon cancer risk utilizing prospectively collected weight data. We included 46,349 men aged 40–75 participating in the Health Professionals Follow-Up Study. Questionnaires including items on weight were completed every second year during follow-up from 1986 to 2004. Updated weight change between consecutive questionnaires during follow-up and recalled weight gain since age 21 was evaluated. All eligible men were cancer-free at baseline. Proportional hazard and restricted spline regression models were implemented. Over an 18-year period, we documented 765 cases of colon cancer. Cumulative mean BMI >22.5 was associated with significantly increased risk of colon cancer. The short-term weight change in the prior 2 to 4 years was positively and significantly associated with risk [HR = 1.14 (95% confidence interval, 1.00–1.29) for 4.54 kg (10 pounds) increment, p = 0.04 for overall trend]. Weight gain per 10 years since age 21 was associated with significantly increased risk [HR = 1.33 (1.12–1.58) for 4.54 kg increase per 10 years, p = 0.001]. We estimated that 29.5% of all colon cancer cases was attributable to BMI above 22.5. Our results add support that overweight and obesity are modifiable risk factors for colon cancer among men and suggest that weight has an important influence on colon cancer risk even in later life.

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“…Ercc2 encodes an ATP-dependent 5'-3' helicase that participates in the opening of the damaged DNA after the damage recognition step in nucleotide excision repair [5,9]. Cyp7a1 is the ratelimiting enzyme that converts cholesterol into cholesterol 7α-hydroxycholesterol in the first step of the classical pathway of bile acid synthesis [47]. Cdkn1a is a major downstream target of p53 and responsible for exerting G1 arrest after DNA is damaged [18].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Hepatocellular Proliferative Activity of Kojic Acid in Mice by a Simultaneous Administration of Ascorbic Acid

Kono

Moto

Muguruma

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. To examine the tumor modification activity of kojic acid (KA) by sodium ascorbic acid (AA), 5-week-old male ICR mice were administered intraperitoneally with N-diethylnitrosamine (DEN) as an initiation treatment. Two weeks after the initiation treatment, animals were fed basal diet containing 0 (Group 1: DEN alone) or 3% KA (Group 3: DEN+KA), drinking water containing 5,000 ppm AA (Group 2: DEN+AA) or 3% KA and 5,000 ppm AA (Group 4: DEN+KA+AA) for 6 weeks. One week after the administration of KA and/or AA, all mice were subjected to two-thirds partial hepatectomy. At the end of the experimental period, all surviving mice were sacrificed and removed the liver. The liver weights of the Groups 3 and 4 were significantly increased, and the number of proliferating cell nuclear antigen positive hepatocytes and the gene expressions of Ccnc, Ccnd1, Ercc and Cyp7a1 were significantly increased in the Group 4, as compared to the Group 1. These results of the present study suggest that AA enhances the hepatocellular proliferative activity of KA in mice. KEY WORDS: ascorbic acid, hepatocarcinogenesis, kojic acid, mouse.J. Vet. Med. Sci. 69(9): 899-908, 2007 Kojic acid (KA; 5-hydroxy-2(hydroxymethyl)-4-pyrone) is a secondary metabolic product of various species of Aspergillus and Penicillium [23]. It is known that this acid inhibits polyphenol oxidase (tyrosinase) in mushrooms, potatoes, apples and crustaceans [41]. Since polyphenol oxidase catalyzes the conversion of tyrosine to melanin via 3,4-dihydroxyphenylalanine and dopaquinone [21], KA has been used as an inhibitor of polyphenol oxidase in food additives for preventing enzymatic browning of raw crabs and shrimps. In addition, because of its excellent skin whitening properties [35] and inhibitory actions on human melanocyte tyrosinase [28], KA has been applied as a cosmetic agent for the purpose of skin lightening.It has been reported that hepatocellular tumors were induced in B6C3F1 mice that were fed diet containing 3% KA for 20 months [14]. In another study, diet containing 0, 1.5 or 3% KA was administered to heterozygous p53-deficient mice of the CBA strain [p53 (+/-) mice] and their wild-type littermates [p53 (+/+) mice] for 26 weeks [50]. In the study, the incidences of hepatocellular adenomas as well as altered hepatocellular foci were increased in p53 (+/-) and p53 (+/+) mice of KA-treated groups with and/or without initiation, as compared to those in the untreated control mice. In our previous confirmation study using CBA wildtype mice, the incidence of proliferative lesions was significantly increased in the liver of mice that were fed diet containing 1% KA for 26 weeks [51]. In addition, it has recently been reported that a 20-week dietary administration of 2% KA increases the number and area of glutathione Stransferase placental (GST-P) form positive foci in the liver of F344 rats [49]. These findings suggest the hepatocarcinogenic potential of KA in the liver of rodent species.With regard to the genotoxicity of KA, several in vitro genotoxici...

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Genetic polymorphism of cholesterol 7α‐hydroxylase (CYP7A1) and colorectal adenomas: Self Defense Forces Health Study

Cited by 18 publications

References 37 publications

Risk Modification of Colorectal Adenoma byCYP7A1Polymorphisms and the Role of Bile Acid Metabolism in Carcinogenesis

Risk Modification of Colorectal Adenoma byCYP7A1Polymorphisms and the Role of Bile Acid Metabolism in Carcinogenesis

Prospective weight change and colon cancer risk in male US health professionals

Enhancement of Hepatocellular Proliferative Activity of Kojic Acid in Mice by a Simultaneous Administration of Ascorbic Acid

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