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Cumulative evidence for relationships between multiple variants in 8q24 and colorectal cancer incidence.

ABSTRACT: Genome-wide association studies (GWAS) have identified multiple independent cancer susceptibility loci at chromosome 8q24.We conducted a comprehensive research synopsis and meta-analysis to evaluate associations between 6 variants in 8q24 and risk of colorectal cancer using data from 31 eligible articles totaling 41,942 cases and 49,968 controls.Of the 6 variants located in 8q24, 3 were significantly associated with risk of colorectal cancer. In particular, both homozygous TT and heterozygous CT genotypes of rs10505477, as well as the GG and TG genotypes of rs6983267, were associated with risk of colorectal cancer.Our study provides summary evidence that common variants in the 8q24 are associated with risk of colorectal cancer in this large-scale research synopsis and meta-analysis. Further studies are needed to explore the exact role of the variants in the 8q24 involved in the etiology of colorectal cancer.

SUBMITTER: Tong Y

PROVIDER: S-EPMC6392673 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Cumulative evidence for relationships between multiple variants in 8q24 and colorectal cancer incidence.

Tong Yu Y Wang Huiqing H Li Shiping S Zhao Fengyan F Ying Junjie J Qu Yi Y Mu Dezhi D

Medicine 20180801 35

Genome-wide association studies (GWAS) have identified multiple independent cancer susceptibility loci at chromosome 8q24.We conducted a comprehensive research synopsis and meta-analysis to evaluate associations between 6 variants in 8q24 and risk of colorectal cancer using data from 31 eligible articles totaling 41,942 cases and 49,968 controls.Of the 6 variants located in 8q24, 3 were significantly associated with risk of colorectal cancer. In particular, both homozygous TT and heterozygous CT ...[more]

PMID: 30170403

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Cumulative evidence of relationships between multiple variants in 8q24 region and cancer incidence.

Project description:Genome-wide association studies (GWAS) have identified multiple independent cancer susceptibility loci at chromosome 8q24. We aimed to evaluate the associations between variants in the 8q24 region and cancer susceptibility. A comprehensive research synopsis and meta-analysis was performed to evaluate associations between 28 variants in 8q24 and risk of 7 cancers using data from 103 eligible articles totaling 146,932 cancer cases and 219,724 controls. Results: 20 variants were significantly associated with risk of prostate cancer, colorectal cancer, thyroid cancer, breast cancer, bladder cancer, stomach cancer, and glioma, including 1 variant associated with prostate cancer, colorectal cancer, and thyroid cancer. Cumulative epidemiological evidence of an association was graded as strong for DG8S737 -8 allele, rs10090154, rs7000448 in prostate cancer, rs10808556 in colorectal cancer, rs55705857 in gliomas, rs9642880 in bladder cancer, moderate for rs16901979, rs1447295, rs6983267, rs7017300, rs7837688, rs1016343, rs620861, rs10086908 associated in prostate cancer, rs10505477, rs6983267 in colorectal cancer, rs6983267 in thyroid cancer, rs13281615 in breast cancer, and rs1447295 in stomach cancer, weak for rs6983561, rs13254738, rs7008482, rs4242384 in prostate cancer. Data from ENCODE suggested that these variants with strong evidence and other correlated variants might fall within putative functional regions. Our study provides summary evidence that common variants in the 8q24 are associated with risk of multiple cancers in this large-scale research synopsis and meta-analysis. Further studies are needed to explore the mechanisms underlying variants in the 8q24 involved in various human cancers.

| S-EPMC7328976 | biostudies-literature

Cumulative Evidence for Relationships Between 8q24 Variants and Prostate Cancer.

Project description:Multiple independent cancer susceptibility loci at chromosome 8q24 have been identified by GWAS (Genome-wide association studies). Forty six articles including 60,293 cases and 62,971 controls were collected to conduct a meta-analysis to evaluate the associations between 21 variants in 8q24 and prostate cancer risk. Of the 21 variants located in 8q2\5 were significantly associated with the risk of prostate cancer. In particular, both homozygous AA and heterozygous CA genotypes of rs16901979, as well as the AA and CA genotypes of rs1447295, were associated with the risk of prostate cancer. Our study showed that variants in the 8q24 region are associated with prostate cancer risk in this large-scale research synopsis and meta-analysis. Further studies are needed to explore the role of the 8q24 variants involved in the etiology of prostate cancer.

| S-EPMC6055007 | biostudies-literature

Cumulative Evidence for Relationships Between Multiple Variants in the TERT and CLPTM1L Region and Risk of Cancer and Non-Cancer Disease

Project description:Background Genetic studies previously reported that variants in TERT-CLPTM1L genes were related to susceptibility of cancer and non-cancer diseases. However, conclusions were not always concordant. Methods We performed meta-analyses to assess correlations between 23 variants within TERT-CLPTM1L region and susceptibility to 12 cancers and 1 non-cancer disease based on data in 109 papers (involving 139,510 cases and 208,530 controls). Two approaches (false-positive report probability test and Venice criteria) were adopted for assessing the cumulative evidence of significant associations. Current study evaluated the potential role of these variants based on data in Encyclopedia of DNA Elements (ENCODE) Project. Results Thirteen variants were statistically associated with susceptibility to 11 cancers and 1 non-cancer disease (p < 0.05). Besides, 12 variants with eight cancers and one non-cancer disease were rated as strong evidence (rs2736098, rs401681, and rs402710 in bladder cancer; rs2736100, rs2853691, and rs401681 in esophageal cancer; rs10069690 in gastric cancer; rs2736100 and rs2853676 in glioma; rs2242652, rs2736098, rs2736100, rs2853677, rs31489, rs401681, rs402710, rs465498, and rs4975616 in lung cancer; rs2736100 in idiopathic pulmonary fibrosis and myeloproliferative neoplasms; and rs401681 in pancreatic and skin cancer). According to data from ENCODE and other public databases, 12 variants with strong evidence might fall within putative functional regions. Conclusions This paper demonstrated that common variants of TERT-CLPTM1L genes were related to susceptibility to bladder, esophageal, gastric, lung, pancreatic, and skin cancer, as well as to glioma, myeloproliferative neoplasms, and idiopathic pulmonary fibrosis, and, besides, the crucial function of the TERT-CLPTM1L region in the genetic predisposition to human diseases is elucidated.

| S-EPMC9279858 | biostudies-literature

Cumulative evidence for relationships between multiple variants of HNF1B and the risk of prostate and endometrial cancers.

Project description:BACKGROUND:To provide a synopsis of the current understanding of the association between variants of HNF1B and cancer susceptibility, we conducted a comprehensive research synopsis and meta-analysis to evaluate associations between HNF1B variants and prostate and endometrial cancers. RESULTS:Eighteen studies totaling 34,937 patients and 55,969 controls were eligible for this meta-analysis. Four variants showed a significant association with the risk of individual cancer. Strong significant associations were found between rs4430796 A and the risk of both prostate cancer (OR =?1.247, p =?2.21?×?10-?77) and endometrial cancer (OR =?1.217, p =?8.98?×?10-?16); the AA, AG genotypes also showed strong significant associations with the risk of prostate cancer (OR1?=?1.517, p =?4.46?×?10-?22; OR2?=?1.180, p =?0.002). There was a strong significant association between rs7501939 G and the risk of prostate cancer (OR =?1.201, p =?9.31?×?10-?31). Strong significant association was found between rs11649743 G (OR =?1.138, p =?1.08?×?10-?12), rs3760511 C (OR =?1.214, p =?1.57?×?10-?19) and the prostate cancer risk;the GG, AG genotypes of rs11649743 also showed strong significant associations with the risk of prostate cancer (OR1?=?1.496, p =?3.32?×?10-?6; OR2?=?1.276, p =?7.82?×?10-?6). All the cumulative epidemiological evidence of associations was graded as strong. CONCLUSIONS:Our study summarizes the evidence and helps to reveal that common variants of HNF1B are associated with risk of prostate and endometrial cancer.

| S-EPMC6062884 | biostudies-literature

Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer.

Project description:Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR?=?0.95, 95% CI?=?0.93-0.97, conditional p?=?5.8 × 10(-6) ), rs7815245 (OR?=?0.94, 95% CI?=?0.91-0.96, conditional p?=?1.1 × 10(-6) ) and rs2033101 (OR?=?1.05, 95% CI?=?1.02-1.07, conditional p?=?1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2) ?=?0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

| S-EPMC5110427 | biostudies-literature

Association between an 8q24 locus and the risk of colorectal cancer in Japanese.

Project description:BACKGROUND: A genome-wide association study (GWAS), which assessed multiple ethnicities, reported an association between single nucleotide polymorphisms in the 8q24 region and colorectal cancer risk. Although the association with the identified loci was strong, information on its impact in combination with lifestyle factors is limited. METHODS: We conducted a case-control study in 481 patients with colorectal cancer (CRC) and 962 sex-age matched non-cancer controls. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Two 8q24 loci, rs6983267 and rs10090154, were assessed by the TaqMan method. Associations were then assessed by multivariate logistic regression models that considered potential confounders. RESULTS: We found an increased risk of CRC with rs6983267 but not with rs10090154. An allelic OR was 1.22 (1.04-1.44, p for trend = 0.014), which remained significant after adjustment for confounders (OR = 1.25). No statistically significant interaction with potential confounding factors was observed. CONCLUSION: The polymorphism rs6983267 showed a significant association with CRC in a Japanese population. Further investigation of the biological mechanism of this association is warranted.

| S-EPMC2783039 | biostudies-literature

Associations between variants of the 8q24 chromosome and nine smoking-related cancer sites.

Project description:Recent genome-wide association studies identified key single nucleotide polymorphisms (SNPs) in the 8q24 region to be associated with prostate cancer. 8q24 SNPs have also been associated with colorectal cancer, suggesting that this region may not be specifically associated to just prostate cancer. To date, the association between these polymorphisms and tobacco smoking-related cancer sites remains unknown. Using epidemiologic data and biological samples previously collected in three case-control studies from U.S. and Chinese populations, we selected and genotyped one SNP from each of the three previously determined "regions" within the 8q24 loci, rs1447295 (region 1), rs16901979 (region 2), and rs6983267 (region 3), and examined their association with cancers of the lung, oropharynx, nasopharynx, larynx, esophagus, stomach, liver, bladder, and kidney. We observed noteworthy associations between rs6983267 and upper aerodigestive tract cancers [adjusted odds ratio (ORadj), 1.69; 95% confidence interval (95% CI), 1.28-2.24], particularly in oropharynx (ORadj, 1.80; 95% CI, 1.30-2.49) and larynx (ORadj, 2.04; 95% CI, 1.12-3.72). We also observed a suggestive association between rs6983267 and liver cancer (ORadj, 1.51; 95% CI, 0.99-2.31). When we stratified our analysis by smoking status, rs6983267 was positively associated with lung cancer among ever-smokers (ORadj, 1.45; 95% CI, 1.05-2.00) and inversely associated with bladder cancer among ever-smokers (ORadj, 0.35; 95% CI, 0.14-0.83). Associations were observed between rs16901979 and upper aerodigestive tract cancer among never-smokers and between rs1447295 and liver cancer among ever-smokers. Our results suggest variants of the 8q24 chromosome may play an important role in smoking-related cancer development. Functional and large epidemiologic studies should be conducted to further investigate the association of 8q24 SNPs with smoking-related cancers.

| S-EPMC2664075 | biostudies-literature

Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer.

Project description:Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P<0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele OR(low) of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction=0.002, adjusted P-interaction=0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.

| S-EPMC2982856 | biostudies-literature

Evidence for an association between prostate cancer and chromosome 8q24 and 10q11 genetic variants in African American men: the Flint Men's Health Study.

Project description:Prostate cancer is the most commonly diagnosed non-skin cancer in men in the United States and the second leading cause of cancer-related mortality. African American men have substantially increased risk of both being diagnosed and dying from the disease. Recent genome-wide genetic association studies have identified a number of common single nucleotide genetic polymorphisms (SNPs) that are associated with prostate cancer in men of European descent. Only a small number of studies have evaluated the association between these genetic variants and prostate cancer in African Americans.We used logistic regression models to assess the association between prostate cancer in African American men and 24 SNPs from regions previously reported to be associated with prostate cancer in men of European descent.We found nominal evidence (P?<?0.05) for association between prostate cancer and three chromosome 8q24 (rs6983561, rs16901979, and rs7000448) and two 10q11 (rs7904463 and rs10740051) SNPs.We confirm recent reports that 8q24 variants identified to be associated with prostate cancer in men of European descent are also associated with prostate cancer in African Americans. Our report is the first to find evidence of association between SNPs near MSMB and prostate cancer in African Americans. Of note, rs7000448 is in strong linkage disequilibrium with rs10761581 in NCOA4, a SNP that has been implicated to be independently associated, with respect to the widely reported SNP rs10993994 in the nearby gene MSMB, with prostate cancer in men of European descent.

| S-EPMC4851861 | biostudies-literature

Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of colorectal cancer.

Project description:BACKGROUND: Genome-wide association studies have identified that genetic variants in 8q24 confer susceptibility to colorectal cancer (CRC). Recently, a novel lncRNA (PRNCR1) that located in the 8q24 was discovered. Single nucleotide polymorphisms (SNPs) in the lncRNAs may influence the process of splicing and stability of mRNA conformation, resulting in the modification of its interacting partners. We hypothesized that SNPs in the lncRNA PRNCR1 may be related to the risk of CRC. METHODS: We conducted a case-control study and genotyped five tag SNPs in the lncRNA PRNCR1 in 908 subjects including 313 cases with CRC and 595 control subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: In overall analyses, we found that the rs13252298 and rs1456315 were associated with significantly decreased risks of CRC. In stratification analyses, we found that CRC patients carrying the rs1456315G were likely to have a tumor size of greater than 5 cm (G vs. A: adjusted OR?=?1.56, 95% CI: 1.10-2.23). Additionally, patients with the rs7007694C and rs16901946G had decreased risks to develop poorly differentiated CRC, whereas patients with the rs1456315G had an increased risk to develop poorly differentiated CRC. CONCLUSION: These findings suggest that SNPs in the lncRNA PRNCR1 may contribute to susceptibility to CRC.

| S-EPMC4029281 | biostudies-literature

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