Much of the Genetic Risk of Colorectal Cancer Is Likely to Be Mediated Through Susceptibility to Adenomas

Carvajal‐Carmona, Luis G.; Zauber, Ann G.; Jones, Angela; Howarth, Kimberley; Wang, Jiping; Cheng, Timothy; Riddell, Robert H.; Lanas, Ángel; Morton, Dion; Bertagnolli, Monica M.; Tomlinson, Ian

doi:10.1053/j.gastro.2012.09.016

Cited by 40 publications

(30 citation statements)

References 15 publications

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“…The association between SNP rs3802842 and CRC has been replicated in at least seven previous studies, with consistent positive associations [17]. Also, SNP rs6983267 has been replicated in at least 14 previous studies in Western populations [18]. Both SNPs have been previously reported in Asian populations but only SNP rs6983267 was found to be associated with rectal cancer in the present study.…”

Section: Genetic Factorssupporting

confidence: 85%

Impaired fasting glucose, single-nucleotide polymorphisms, and risk for colorectal cancer in Koreans

2016

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OBJECTIVES:Numerous studies have demonstrated that fasting serum glucose (FSG) levels and certain single-nucleotide polymorphisms (SNPs) are related to an increased risk of colorectal cancer (CRC); however, their combined effects are still unclear. METHODS:Of a total of 144,527 men and women free of cancer at baseline, 317 developed CRC during 5.3 years of follow-up. A case-cohort study (n = 1,691) was used, consisting of participants with a DNA sample available. Three well-known SNPs (rs3802842, rs6983267, rs10795668) were genotyped. Hazard ratios (HR) and 95% confidence intervals (CI) of CRC, colon and rectal cancer were calculated, with the Cox proportional hazard models. RESULTS:The crude incidence rates per 100,000 person-years were 41.1 overall, 48.4 for men, and 29.3 for women. Among participants with dysglycemia, SNPs rs3802842 and rs6983267 were both associated with an increased risk of CRC (HR, 3.2; 95% CI, 1.9 to 5.5 and HR, 1.8; 95% CI, 1.1 to 3.1, respectively) and rectal cancer (HR, 3.4; 95% CI, 1.8 to 6.6 and HR, 3.3; 95% CI, 1.6 to 7.1, respectively). The interaction effect of dysglycemia and SNPs was positive, that is, resulted in an elevated risk of CRC, but was not statistically significant. CONCLUSIONS:This study demonstrates that both high FSG and certain SNPs are major risk factors for CRC and rectal cancer but that they did not interact synergistically. The difference in effect size of the SNPs according to CRC subtype (i.e., colon or rectal cancer) and presence of dysglycemia merits further research.

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Section: Genetic Factorssupporting

confidence: 85%

Impaired fasting glucose, single-nucleotide polymorphisms, and risk for colorectal cancer in Koreans

2016

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“…A variant in chromosome 8q24 initially described by admixture mapping for prostate cancer in African Americans also showed a positive association with colorectal cancer risk 30 and, recently, a case-control study reported an association of one 8q24 loci variant (rs380284) and adenoma risk in Caucasians. 39 In conclusion, we report for the first time that African ancestry (or variants linked to it) contributes to the susceptibility of colorectal cancer in admixed Latin American population. Our results are promising as they may help get insights of colorectal carcinogenesis and even more to find biomarkers useful to stratify colorectal cancer risk in the Latino populations, where colorectal mortality rates are increasing, although not high enough to recommend mass screening programs.…”

Section: Discussionmentioning

confidence: 65%

“…The positive association of African genetic ancestry with adenoma and colorectal cancer is consistent with a recent publication reporting that colorectal cancer risk is likely to be mediated through genetic susceptibility to adenomas. 39 Early detection of adenomas is a key issue in colorectal cancer control. Newly published evidence supports that detecting adenomas and removing them not only decreases the incidence but also the mortality of colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations

et al. 2014

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Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age-and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI) ¼ 0.11-0.15) and cancer cases (0.14, 95% CI ¼ 0.12-0.16) compared with controls (0.11, 95% CI ¼ 0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR) ¼ 1.12, 95% CI ¼ 0.97-1.30) and adenocarcinoma (OR ¼ 1.19, 95% CI ¼ 1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population.

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“…It is possible that these results reflect different variant alleles in the populations studied, given that the minor allele frequency was different. The rs4939827 SNP likely influences cancer via inhibition of SMAD7 [28,29] , a component of the transforming growth factor-β signalling pathway that regulates growth and apoptosis and plays an important role in cancer initiation and progression [30][31][32][33] . Despite the adequate statistical power of the current study, some limitations should be considered.…”

Section: Discussionmentioning

confidence: 99%

“…Second, the association between genetic polymorphism and clinicopathologic type (adenocarcinoma or squamous cell carcinoma) was not evaluated. This could be an important factor, as rs4444235 and rs4939827 were shown to be over-represented in CRC-free patients with adenomas [32,33] .In conclusion, this association study investigated 31 SNPs identified from CRC GWAS as genetic susceptibility factors for esophageal cancer in a Chinese population. The replication of genetic associations from CRC to esophageal cancer highlights the utility of case-control studies to confirm novel associations characterized in large GWAS of digestive system diseases.…”

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confidence: 92%

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population

Geng

Xun

et al. 2015

WJG

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AIM:To investigate the association between colorectal cancer (CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population. METHODS:A case-control study was conducted including 360 esophageal cancer patients and 310 healthy controls. Thirty-one single-nucleotide polymorphisms (SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from HardyWeinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ 2 test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models (codominant, dominant, recessive, overdominant, and additive). ORs and 95%CIs were calculated by unconditional logistic regression with adjustments for age and sex. RESULTS:The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold (95%CI: ORIGINAL ARTICLE Case Control StudyAssociation of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population of esophageal cancer, squamous cell carcinoma is the most common, and prognosis highly correlates with disease stage and advancement.Epidemiologic studies indicate that tobacco smoking, alcohol intake, nutritional deficiencies, and dietary carcinogen exposure contribute to the etiology of esophageal cancer [4,5] . However, only a small proportion of individuals exposed to these factors actually develop esophageal cancer, suggesting that genetic factors also play a vital role in susceptibility. It has been reported that susceptibility to esophageal cancer is not dependent on a single gene and is affected by population differences [6,7] . Colorectal cancer (CRC) is the most common malignant tumor of the digestive tract, and the second most common of all gastrointestinal tumors [8] . Recent studies have identified haplotype-tagging singlenucleotide polymorphisms (SNPs) that are associated with an increased colorectal cancer risk in the general population [9][10][11][12] . Previous genetic polymorphism studies in the Chinese population were focused solely on SNPs associated with esophageal cancer risk in genome-wide association studies (GWAS) [13][14][15] . The purpose of the present study was to identify digestive system tumor common susceptibility loci. To achieve this, 31 high-frequency SNPs associated with CRC risk in the Chinese population were evaluated with respect to esophageal cancer risk. MATERIALS AND METHODS Study participantsAll participants were Chinese Han that were seen between January 2011 and February 2014 at the First Affiliated Hospital of the Medical College of Xi'an Jiaotong University. None of the study participants received neoadjuvant therapy or had previous histories of other cancers, chemotherapy, or radiotherapy. Participants were chosen without restrictions of age, sex, or disease stage. None of the healthy control subjects had a...

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Much of the Genetic Risk of Colorectal Cancer Is Likely to Be Mediated Through Susceptibility to Adenomas

Cited by 40 publications

References 15 publications

Impaired fasting glucose, single-nucleotide polymorphisms, and risk for colorectal cancer in Koreans

Impaired fasting glucose, single-nucleotide polymorphisms, and risk for colorectal cancer in Koreans

Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population

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