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Genome-Wide Association Studies and Colorectal Cancer

Loïc Le Marchand
2009 Surgical Oncology Clinics of North America  
Genome-wide association studies (GWAS) provide a powerful new approach to identify common, low-penetrance susceptibility loci without prior knowledge of biological function. Results from three GWAS conducted in populations of European ancestry are available for colorectal cancer (CRC). These studies have identified eleven disease loci which, for the majority, were not previously suspected to be related to CRC. The proportions of the familial and population risks explained by these loci are
more » ... and they currently are not useful for risk prediction. However, the power of these studies was low indicating that a number of other loci may be identified in new on-going GWAS, and in pooled analyses. Thus, the risk prediction ability of susceptibility markers identified in GWAS for CRC may improve as more variants are discovered. This may in turn have important implications for targeting high risk individuals for colonoscopy screening.
doi:10.1016/j.soc.2009.07.004 pmid:19793573 pmcid:PMC2756243 fatcat:5xve2zun6fbsdaexb47n7p2wqe

Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

Yumie Takata, Gertraud Maskarinec, Loïc Le Marchand
2007 BMC Cancer  
Mammographic density is a strong predictor of breast cancer risk and is increased by hormone replacement therapy (HRT). Some associations with genetic polymorphisms in enzymes involved in estrogen metabolism have been described. This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val 58 Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort. Methods: Mammographic density, before
more » ... agnosis in cases, was quantified by using a validated computer-assisted method. Blood samples were genotyped by standard PCR/RFLP methods. Adjusted mean percent density was calculated by genotype using mixed models with the unstructured covariance option. Results: A positive association between the C allele in the CYP1A2*1F gene and percent density, but not the dense area, was suggested (p = 0.11). The relation was limited to controls (p = 0.045), postmenopausal women not using HRT (p = 0.08), and normal weight subjects (p = 0.046). We did not observe any relation between the COMT Val 58 Met polymorphism and breast density. Conclusion: The lack of an association between the CYP1A2 genotype and the size of the dense areas suggests an effect on the non-dense, i.e., fatty breast tissue. The discrepancies among studies may be due to differential susceptibility; changes in enzyme activity as a result of the CYP1A2*1F polymorphism may influence breast tissue differently depending on hormonal status. Larger studies with the ability to look at interactions would be useful to elucidate the influence of genetic variation in CYP1A2 and COMT on the risk of developing breast cancer.
doi:10.1186/1471-2407-7-30 pmid:17295924 pmcid:PMC1800856 fatcat:yekfcdwex5a3xiebatucw2etxi

The role of heterocyclic aromatic amines in colorectal cancer: the evidence from epidemiologic studies

Loïc Le Marchand
2021 Genes and Environment  
AbstractSince Dr. Sugimura's discovery of heterocyclic aromatic amines (HAA) in broiled fish, many epidemiological studies have been conducted to investigate their role in human cancers, often focusing on colorectal cancer. The difficulty in measuring HAA exposure from meat and fish intake in these studies has resulted in inconsistent findings. Because studying individuals who may be particularly susceptible to the carcinogenic effects of HAA might facilitate the demonstration of a link with
more » ... cer, multiple studies have focused on individuals with the high activity phenotype for CYP1A2 and/or NAT2, the two main metabolic enzymes involved in the bioactivation of HAA. These investigations have also yielded inconsistent results. Two recent large pooled analyses of colorectal cancer studies have helped clarify the overall evidence. One was conducted in whites and reported no interaction of red meat intake and NAT2 genotype on risk in Whites. The other was conducted in Japanese and African Americans, two populations with high rates of the disease and a prevalence of the at-risk rapid NAT2 phenotype 10- and 2-fold greater than in whites, respectively. In those groups, a significant interaction was found, with the association of red meat with colorectal cancer being strongest among individuals with the rapid NAT2 phenotype, intermediate among those with the intermediate phenotype and not significant among those with the slow NAT2 phenotype. Recent research on biomarkers has focused on PhIP hair content, as a marker of exposure to HAA, and on DNA adducts using new sensitive quantitative methods, as markers of early biological effects. These advances, when brought to bear, may contribute greatly to the further elucidation of the carcinogenicity of HAA in humans.
doi:10.1186/s41021-021-00197-z pmid:34099058 fatcat:zin6sistqnhhflwo73mwuvmuky

Prospective Study of Alcohol Drinking, Smoking, and Pancreatitis

Veronica Wendy Setiawan, Stephen J. Pandol, Jacqueline Porcel, Lynne R. Wilkens, Loïc Le Marchand, Malcolm C. Pike, Kristine R. Monroe
2016 Pancreas  
Objectives-We conducted a prospective analysis of 145,886 participants in the Multiethnic Cohort to examine the relationship of alcohol drinking and smoking with pancreatitis. Methods-Pancreatitis cases were categorized as gallstone-related acute pancreatitis (GS AP) (N=1,065), non-GS AP (N=1,222), and recurrent acute (RAP)/chronic pancreatitis (CP) (N=523). We used the baseline questionnaire to identify alcohol intake and smoking history. Associations were estimated by hazard ratios (HRs) and
more » ... 5% confidence intervals (CIs) using Cox models. Results-Cigarette smoking was associated with non-GS AP and RAP/CP. Moderate alcohol intake was inversely associated with all types of pancreatitis in women (HRs=0.66 to 0.81 for <1 drink/day), and with RAP/CP in men (HR=0.57; 95% CI: 0.41, 0.79 for <2 drinks/day). The risk of non-GS pancreatitis associated with current smoking was highest among men who consumed >4 drinks/day (HR=2.06; 95% CI: 1.28, 3.30), while among never-smokers, moderate drinking was associated with a reduced risk (HR=0.70; 95% CI: 0.51, 0.96). In women, drinking <2 drinks/day was associated with a reduced risk of GS-AP among never smokers (HR=0.61; 95% CI: 0.46, 0.80). Conclusions-Smoking is a risk factor for non-GS pancreatitis. Moderate alcohol intake is protective against all types of pancreatitis in women and against RAP/CP in men.
doi:10.1097/mpa.0000000000000657 pmid:27171516 pmcid:PMC4905778 fatcat:fakwziymdrgvrltskjytaorgi4

Asian Adolescents Have a Higher Trunk:Peripheral Fat Ratio than Whites

Rachel Novotny, Yihe G. Daida, John S. Grove, Loïc Le Marchand, Vinutha Vijayadeva
2006 Journal of Nutrition  
Body fat, especially in the upper body, has been associated with increased risk of chronic disease among adults. Factors associated with these traits among ethnically diverse populations are not well studied. We examined factors influencing body fat and weight among Asian and White adolescent girls from the female adolescent maturation longitudinal study (initial exam plus 2-y follow-up examination) in Hawaii. The objective of this study was to identify and compare influences on and differences
more » ... in body size and fat distribution among Asian and White adolescent girls. Subjects were identified among age-eligible members of a large HMO. Of the 214 girls recruited for Exam 1, 107 girls returned for Exam 2. The girls' age, ethnicity, a 3-d diet record, and physical activity recall were obtained by questionnaire at both times, and Tanner pubic hair stage and anthropometry were clinically measured by trained staff at both exams. The ethnic proportion of the study sample was 57% Asian and 43% White. Each girl's ethnicity was based on the ethnic proportion of each biologic parent. The percentage of body fat was measured by Lunar Prodigy dual energy X-ray absorptiometry (DXA) at the follow-up exam only. Among various measures of skeletal size and adiposity, only leg length (inversely) and DXA trunk:peripheral fat ratio (directly) were associated with proportion of Asian ethnicity, after adjusting for age, Tanner pubic hair stage, physical activity, and energy intake. In a multivariate analysis focusing on the trunk:peripheral fat ratio, this measure of central obesity was positively associated with proportion of Asian ethnicity (P = 0.001) and bi-iliac breadth (P = 0.002), and negatively associated with birth weight (P = 0.021), after adjustment for Tanner pubic hair stage, physical activity, energy intake, biacromial breadth, and height. In conclusion, Asian adolescents have a higher trunk:peripheral fat ratio than Whites. Adolescent bi-iliac breadth (positively) and birthweight (negatively) are associated with more body fat on the trunk vs. periphery during adolescence.
doi:10.1093/jn/136.3.642 pmid:16484537 pmcid:PMC1478165 fatcat:2ayoxivojnf2pnoczpukuo3qze

Cigarette smoking and colorectal cancer mortality among 602,242 Norwegian males and females

Inger Torhild Gram, Ranjan Parajuli, Eivind Bjerkaas, Aage Tverdal, Loic Le Marchand, Elisabete Weiderpass
2014 Clinical Epidemiology  
Colorectal cancer (CRC) is one of the main cancer types, with high incidence and mortality in Norway. We examined the association between different measures of smoking exposure and CRC mortality overall and by subsite in a large Norwegian cohort. Methods: We followed 602,242 participants from four Norwegian health surveys, aged 19-67 years at enrollment between 1972 and 2003 by linkage to the national registries through December 2007. We used Cox proportional hazard models to estimate hazard
more » ... ios (HRs) and 95% confidence intervals (CIs) by smoking categories for different CRC endpoints. Results: During a mean follow-up of 14 years, 2,333 Norwegian males and females died of CRC (60% men). Male and female ever smokers had a 20% (HR 1.23, CI 1.08-1.40 and HR 1.22, 95% CI 1.06-1.40, respectively) increased risk of death from CRC compared with sex-specific never smokers. For proximal colon cancer mortality, female ever smokers had a 50% (HR 1.49, 95% CI 1.20-1.87) increased risk compared with female never smokers. The increased risk of rectal cancer mortality was about 40% higher for male ever smokers (HR 1.43, 95% CI 1.14-1.81) compared with male never smokers. A test for heterogeneity by sex showed an increased risk of rectal cancer mortality among men which was significant for former smokers (Wald χ 2 =0.02) and an increased risk of proximal colon cancer mortality among women which was significant for ever and former smokers (Wald χ 2 =0.02 and χ 2 =0.04, respectively). Conclusion: Smoking is associated with increased CRC mortality in both sexes. The risk of rectal and proximal colon cancer mortality was most pronounced among male and female smokers respectively.
doi:10.2147/clep.s58722 pmid:24741327 pmcid:PMC3984060 fatcat:bdarha55tngyje2xgxrui7q3zy

Dietary Intake Mediates Ethnic Differences in Gut Microbial Composition

Kirra Borrello, Unhee Lim, Song-Yi Park, Kristine R. Monroe, Gertraud Maskarinec, Carol J. Boushey, Lynne R. Wilkens, Timothy W. Randolph, Loïc Le Le Marchand, Meredith A. Hullar, Johanna W. Lampe
2022 Nutrients  
The human gut microbiome (GM) has been observed to vary by race/ethnicity. Objective: Assess whether racial/ethnic GM variation is mediated by differences in diet. Design: Stool samples collected from 2013 to 2016 from 5267 healthy Multiethnic Cohort participants (age 59–98) were analyzed using 16S rRNA gene sequencing to estimate the relative abundance of 152 bacterial genera. For 63 prevalent genera (>50% in each ethnic group), we analyzed the mediation of GM differences among African
more » ... s, Japanese Americans, Latinos, Native Hawaiians, and Whites by overall diet quality (Healthy Eating Index score (HEI-2015)) and intake amounts of 14 component foods/nutrients assessed from 2003 to 2008. For each significant mediation (p < 1.3 × 10-5), we determined the percent of the total ethnicity effect on genus abundance mediated by the dietary factor. Results: Ethnic differences in the abundance of 12 genera were significantly mediated by one or more of eight dietary factors, most frequently by overall diet quality and intakes of vegetables and red meat. Lower vegetable intake mediated differences in Lachnospira (36% in African Americans, 39% in Latinos) and Ruminococcus-1 (−35% in African Americans, −43% in Latinos) compared to Native Hawaiians who consumed the highest amount. Higher red meat intake mediated differences in Lachnospira (−41%) and Ruminococcus-1 (36%) in Native Hawaiians over African Americans, who consumed the least. Dairy and alcohol intakes appeared to mediate and counterbalance the difference in Bifidobacterium between Whites and Japanese Americans. Conclusions: Overall diet quality and component food intakes may contribute to ethnic differences in GM composition and to GM-related racial/ethnic health disparities.
doi:10.3390/nu14030660 pmid:35277019 pmcid:PMC8840192 fatcat:aucial7r2zeexd4sy7bxd4b2zy

Cigarette smoking and risk of colorectal cancer among Norwegian women

Inger T. Gram, Tonje Braaten, Eiliv Lund, Loic Le Marchand, Elisabete Weiderpass
2009 Cancer Causes and Control  
Objective The association between cigarette smoking and colorectal cancer (CRC) is still not established. In 2002, Norwegian women had the second highest incidence of CRC in the world. A large proportion of Norwegian women are ever smokers. We examined the association between cigarette smoking and CRC incidence among Norwegian women. Methods We followed 68,160 women, aged 30-69 years, from the Norwegian Women and Cancer Study who completed a questionnaire in 1996 or 1998 by linkages to national
more » ... registers through 31 December 2005. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazard models. Subsequently, we estimated the population attributable fraction. Results Altogether, 425 incident cases of primary, invasive CRC were identified. Ever smokers had a 20% increased risk of CRC (RR = 1.2; 95% CI = 1.0-1.5), a 30% increased risk of colon (RR = 1.3; 95% CI = 1.0-1.7), and a 10% increased risk of rectal (RR = 1.1; 95% CI = 0.7-1.5) cancer compared to never smokers. The population attributable fraction was estimated to be 12% which indicated that approximately one in eight of the CRC cases could have been prevented at a population level. Conclusion Our results support the hypothesis that cigarette smoking is a preventable cause of CRC among women.
doi:10.1007/s10552-009-9327-x pmid:19274482 pmcid:PMC2694321 fatcat:wmyvqgvgtnhz5bgwg65tnykuse

In silico pathway analysis and tissue specific cis-eQTL for colorectal cancer GWAS risk variants

Lenora W. M. Loo, Mathieu Lemire, Loïc Le Marchand
2017 BMC Genomics  
Genome-wide association studies have identified 55 genetic variants associated with colorectal cancer risk to date. However, potential causal genes and pathways regulated by these risk variants remain to be characterized. Therefore, we performed gene ontology enrichment and pathway analyses to determine if there was an enrichment of genes in proximity to the colorectal cancer risk variants that could further elucidate the probable causal genes and pathways involved in colorectal cancer biology.
more » ... Results: For the 65 unique genes that either contained, or were immediately neighboring up-and downstream, of these variants there was a significant enrichment for the KEGG pathway, Pathways in Cancer (p-value = 2.67 × 10 −5 ) and an enrichment for multiple biological processes (FDR < 0.05), such as cell junction organization, tissue morphogenesis, regulation of SMAD protein phosphorylation, and odontogenesis identified through Gene Ontology analysis. To identify potential causal genes, we conducted a cis-expression quantitative trait loci (cis-eQTL) analysis using gene expression and genotype data from the Genotype-Tissue Expression (GTEx) Project portal in normal sigmoid (n = 124) and transverse (n = 169) colon tissue. In addition, we also did a cis-eQTL analysis on colorectal tumor tissue (n = 147) from The Cancer Genome Atlas (TCGA). We identified two risk alleles that were significant cis-eQTLs for FADS2 (rs1535) and COLCA1 and 2 (rs3802842) genes in the normal transverse colon tissue and two risk alleles that were significant cis-eQTLs for the CABLES2 (rs2427308) and LIPG (rs7229639) genes in the normal sigmoid colon tissue, but not tumor tissue. Conclusions: Our data reaffirm the potential to identify an enrichment for biological processes and candidate causal genes based on expression profiles correlated with genetic risk alleles of colorectal cancer, however, the identification of these significant cis-eQTLs is context and tissue specific.
doi:10.1186/s12864-017-3750-2 pmid:28506205 pmcid:PMC5432975 fatcat:pvedgrmeu5gstpncekomyr327m

Smoking related lung cancer mortality by education and sex in Norway

Merethe S. Hansen, Idlir Licaj, Tonje Braaten, Arnulf Langhammer, Loic Le Marchand, Inger Torhild Gram
2019 BMC Cancer  
doi:10.1186/s12885-019-6330-9 pmid:31752755 pmcid:PMC6873553 fatcat:j23njzqgrrhedk2dsttq2mhiiy

In Silico Functional Pathway Annotation of 86 Established Prostate Cancer Risk Variants

Lenora W. M. Loo, Aaron Y. W. Fong, Iona Cheng, Loïc Le Marchand, Allen Gao
2015 PLoS ONE  
Heritability is one of the strongest risk factors of prostate cancer, emphasizing the importance of the genetic contribution towards prostate cancer risk. To date, 86 established prostate cancer risk variants have been identified by genome-wide association studies (GWAS). To determine if these risk variants are located near genes that interact together in biological networks or pathways contributing to prostate cancer initiation or progression, we generated gene sets based on proximity to the
more » ... prostate cancer risk variants. We took two approaches to generate gene lists. The first strategy included all immediate flanking genes, up-and downstream of the risk variant, regardless of distance from the index variant, and the second strategy included genes closest to the index GWAS marker and to variants in high LD (r 2 0.8 in Europeans) with the index variant, within a 100 kb window up-and downstream. Pathway mapping of the two gene sets supported the importance of the androgen receptor-mediated signaling in prostate cancer biology. In addition, the hedgehog and Wnt/β-catenin signaling pathways were identified in pathway mapping for the flanking gene set. We also used the HaploReg resource to examine the 86 risk loci and variants high LD (r 2 0.8) for functional elements. We found that there was a 12.8 fold (p = 2.9 x 10 -4 ) enrichment for enhancer motifs in a stem cell line and a 4.4 fold (p = 1.1 x 10 -3 ) enrichment of DNase hypersensitivity in a prostate adenocarcinoma cell line, indicating that the risk and correlated variants are enriched for transcriptional regulatory motifs. Our pathway-based functional annotation of the prostate cancer risk variants highlights the potential regulatory function that GWAS risk markers, and their highly correlated variants, exert on genes. Our study also shows that these genes may function cooperatively in key signaling pathways in prostate cancer biology.
doi:10.1371/journal.pone.0117873 pmid:25658610 pmcid:PMC4320069 fatcat:hi4jbn3wvfcyzn2wba23gdofu4

Ethnic differences in excretion of butadiene-DNA adducts by current smokers

Caitlin C Jokipii Krueger, S Lani Park, Guru Madugundu, Yesha Patel, Loic Le Marchand, Daniel O Stram, Natalia Tretyakova
2021 Carcinogenesis  
1,3-butadiene (BD) is a known human carcinogen used in the synthetic polymer industry and also found in cigarette smoke, automobile exhaust, and wood burning smoke. BD is metabolically activated by cytochrome P450 monooxygenases (CYP) 2E1 and 2A6 to 3,4-epoxy-1-butene (EB), which can be detoxified by GST-catalyzed glutathione conjugation or hydrolysis. We have previously observed ethnic differences in urinary levels of EB-mercapturic acids in white, Japanese American, and Native Hawaiian
more » ... . In the present study, similar analyses were extended to urinary BD-DNA adducts. BD-induced N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts were quantified in urine samples obtained from smokers and non-smokers belonging to three racial/ethnic groups: white, Japanese American, and Native Hawaiian. After adjusting for sex, age, nicotine equivalents, BMI, and batch, we found that Japanese American smokers excreted significantly higher amounts of urinary EB-GII than whites (1.45 [95%CI: 1.12–1.87] vs 0.68 [95%CI: 0.52–0.85] fmol/mL urine, p=4x10 -5). Levels of urinary EB-GII in Native Hawaiian smokers were not different from those in whites (0.67 [95%CI: 0.51–0.84] fmol/mL urine, p=0.938). There were no racial/ethnic differences in urinary EB-GII adduct levels in non-smokers. Racial/ethnic differences in urinary EB-GII adduct levels in smokers could not be explained by GSTT1 gene deletion or CYP2A6 enzymatic activity. Urinary EB-GII adduct levels in smokers were significantly associated with concentrations of BD metabolite dihyroxybutyl mercapturic acid (DHBMA). Overall, our results reveal that urinary EB-GII adducts in smokers differ across racial/ethnic groups. Future studies are required to understand other genetic and epigenetic factors that may be responsible for these differences.
doi:10.1093/carcin/bgab020 pmid:33693566 pmcid:PMC8163050 fatcat:pva464tv6rbshg5j6qpcwoksk4

Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk

Loïc Le Marchand, Timothy Donlon, Annette Lum-Jones, Ann Seifried, Lynne R Wilkens
2002 Cancer Epidemiology, Biomarkers and Prevention  
Oxidative stress may be one mechanism by which tobacco smoke causes lung cancer. A common oxidative damage to DNA is the highly mutagenic 7,8-dihydro-8-oxoguanine adduct, which can be repaired by 8-oxoguanine glycosylase I (OGG1). A Ser326Cys substitution polymorphism in the hOGG1 gene has been suggested, based on in vitro data, to reduce the activity of the enzyme. We tested the association of this polymorphism with lung cancer in a population-based, case control study of 298 cases and 405
more » ... rols of Caucasian, Japanese, or Native Hawaiian ancestry in Hawaii. Subjects were genotyped with a PCR-RFLP assay, and odds ratios were estimated by logistic regression after adjustment for other observed risk factors, including smoking and vegetable intake. We found marked differences in the frequencies of the hOGG1 Cys variant allele among ethnic groups (45% in Hawaiians, 42% in Japanese, and 22% in Caucasians). The homozygous Cys/Cys genotype was also found to be more common in cases than controls (P = 0.008), with an odds ratio of 2.1 (95% confidence interval: 1.2-3.7) for this genotype compared with the Ser/Ser genotype. Heterozygous individuals were not at increased risk. This association with the Cys/Cys genotype was observed for each sex, ethnic group, and lung cancer cell type. There was also the suggestion that vegetable intake may not be protective against lung cancer among subjects with the Cys/Cys genotype. These data suggest that the presence of two hOGG1 326Cys alleles confers a 2-fold increased risk of lung cancer. Additional studies need to be conducted to confirm this association.
pmid:11927502 fatcat:arxxrgfswja5pibuquayq4rlja

Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk

Loïc Le Marchand, Timothy Donlon, Ann Seifried, Lynne R Wilkens
2002 Cancer Epidemiology, Biomarkers and Prevention  
N-Nitroso compounds are suspected colorectal cancer (CRC) carcinogens to which individuals on a diet high in red meat (RM) may be particularly exposed. Many of these compounds undergo alpha-hydroxylation by CYP2E1 to form DNA adducts. The gene coding for this enzyme is polymorphic and thus may constitute a susceptibility factor for CRC. We conducted a population-based case-control study in Hawaii to test the association of two functional polymorphisms in CYP2E1 (the G1259C RsaI substitution and
more » ... a 5' 96-bp insertion variant) with CRC, as well as their modifying effects on the association of RM and processed meat (PM) with this cancer. We obtained interviews and blood samples for 521 patients with CRC (165 with rectal cancer) and 639 controls of Japanese, Caucasian, or Hawaiian origin. Genotyping was performed by PCR. After adjustment for CRC risk factors, subjects with the 5' insert variant were found to be at a 60% increased risk (95% confidence interval, 1.1-2.5) for rectal cancer. Subjects who carry the insert and who were predicted to have been exposed to increased levels of nitrosamines, based on their high intake of RM or PM, were at a markedly greater increased risk (2- and 3-fold for RM and PM, respectively) for rectal cancer. No clear association was found for colon cancer. A similar increase in rectal cancer risk was found for CYP2E1 insert carriers who consumed salted/dried fish or Oriental pickled vegetables. These data provide additional support for the hypothesis that nitrosamines are carcinogenic to the rectum in humans and that RM and, in particular, PMs are significant sources of exposure for these compounds.
pmid:12376502 fatcat:pxbbpeun4betpahx2eb74ym2fm

Reply to High hepatocellular carcinoma risk among US-born Hispanics

V. Wendy Setiawan, Pengxiao C. Wei, Brenda Y. Hernandez, Shelly C. Lu, Kristine R. Monroe, Loic Le Marchand, Jian Min Yuan
2016 Cancer  
We appreciate the interest from Drs. Antonio Ponzetto and Natale Figura in our paper reporting the unexplained greater incidence of hepatocellular carcinoma (HCC) in US-born Hispanic men 1 . Ponzetto and Figura proposed that Helicobacter pylori (H. pylori), particularly the CagA + strain, might be responsible for the excess HCC risk observed among US-born Hispanic men. Waluga et al 2 recently summarized the current knowledge on the possible role of H. pylori infection and other Helicobacter
more » ... ies in liver disease etiology, including HCC. The proposed mechanisms through which H. pylori impacts the development of HCC are undoubtedly complex and studies have supported H. pylori's involvement in the pathogenesis of HCC, while others have not 2 . A 2005 study showed that the prevalence of H. pylori infection among Hispanics in California has declined with more recent generations in the US 3 . Hispanic immigrants had the highest prevalence (31%), first generation US-born Hispanics had an intermediate prevalence (9%), and second generation US-born Hispanics had the lowest prevalence (3%) 3 .
doi:10.1002/cncr.30396 pmid:27741358 pmcid:PMC5222752 fatcat:whcxarz3l5ah3mfapmbxaj7r3m
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