Browsing by Author "Potter JD"
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- ItemA perspective on green, blue, and grey spaces, biodiversity, microbiota, and human health.(Elsevier B.V., 2023-09-20) Potter JD; Brooks C; Donovan G; Cunningham C; Douwes JHumans have lived from equator to poles for millennia but are now increasingly intruding into the wild spaces of other species and steadily extruding ourselves from our own wild spaces, with a profound impact on: our relationship with the natural world; survival of other species; pollution; climate change; etc. We have yet to grasp how these changes directly impact our own health. The primary focus of this paper is on the beneficial influence of proximity to the natural environment. We summarize the evidence for associations between exposure to green space and blue space and improvements in health. In contrast, grey space - the urban landscape - largely presents hazards as well as reducing exposure to green and blue space and isolating us from the natural environment. We discuss various hypotheses that might explain why green, blue, and grey space affect health and focus particularly on the importance of the biodiversity hypothesis and the role of microbiota. We discuss possible mechanisms and exposure routes - air, soil, and water. We highlight the problem of exposure assessment, noting that many of our current tools are not fit for the purpose of understanding exposure to green and blue space, aerosols, soils, and water. We briefly discuss possible differences between indigenous perspectives on the nature of our relationship with the environment and the more dominant international-science view. Finally, we present research gaps and discuss future directions, particularly focusing on the ways in which we might - even in the absence of a full understanding of the mechanisms by which blue, green, and grey space affect our health - begin to implement policies to restore some balance to our environment of with the aim of reducing the large global burden of ill health.
- ItemAcceptability of human papillomavirus (HPV) self-sampling among never- and under-screened Indigenous and other minority women: a randomised three-arm community trial in Aotearoa New Zealand.(Elsevier Ltd, 2021-11) Brewer N; Bartholomew K; Grant J; Maxwell A; McPherson G; Wihongi H; Bromhead C; Scott N; Crengle S; Foliaki S; Cunningham C; Douwes J; Potter JDBACKGROUND: Internationally, self-sampling for human papillomavirus (HPV) has been shown to increase participation in cervical-cancer screening. In Aotearoa New Zealand, there are long-standing ethnic inequalities in cervical-cancer screening, incidence, and mortality, particularly for indigenous Māori women, as well as Pacific and Asian women. METHODS: We invited never- and markedly under-screened (≥5 years overdue) 30-69-year-old Māori, Pacific, and Asian women to participate in an open-label, three-arm, community-based, randomised controlled trial, with a nested sub-study. We aimed to assess whether two specific invitation methods for self-sampling improved screening participation over usual care among the least medically served populations. Women were individually randomised 3:3:1 to: clinic-based self-sampling (CLINIC - invited to take a self-sample at their usual general practice); home-based self-sampling (HOME - mailed a kit and invited to take a self-sample at home); and usual care (USUAL - invited to attend a clinic for collection of a standard cytology sample). Neither participants nor research staff could be blinded to the intervention. In a subset of general practices, women who did not participate within three months of invitation were opportunistically invited to take a self-sample, either next time they attended a clinic or by mail. FINDINGS: We randomised 3,553 women: 1,574 to CLINIC, 1,467 to HOME, and 512 to USUAL. Participation was highest in HOME (14.6% among Māori, 8.8% among Pacific, and 18.5% among Asian) with CLINIC (7.0%, 5.3% and 6.9%, respectively) and USUAL (2.0%, 1.7% and 4.5%, respectively) being lower. In fully adjusted models, participation was statistically significantly more likely in HOME than USUAL: Māori OR=9.7, (95%CI 3.0-31.5); Pacific OR=6.0 (1.8-19.5); and Asian OR=5.1 (2.4-10.9). There were no adverse outcomes reported. After three months, 2,780 non-responding women were invited to participate in a non-randomised, opportunistic, follow-on substudy. After 6 months,192 (6.9%) additional women had taken a self-sample. INTERPRETATION: Using recruitment methods that mimic usual practice, we provide critical evidence that self-sampling increases screening among the groups of women (never and under-screened) who experience the most barriers in Aotearoa New Zealand, although the absolute level of participation through this population approach was modest. Follow-up for most women was routine but a small proportion required intensive support. TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12618000367246 (date registered 12/3/2018) https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371741&isReview=true; UTN: U1111-1189-0531. FUNDING: Health Research Council of New Zealand (HRC 16/405). PROTOCOL: http://publichealth.massey.ac.nz/assets/Uploads/Study-protocol-V2.1Self-sampling-for-HPV-screening-a-community-trial.pdf.
- ItemAlcohol and Gastrointestinal Cancers in Korea-Risk, Inactive Genes, and Missing Alcohol(American Medical Association, 2021-08-18) Potter JD
- ItemAssociation of Sleep Duration With All- and Major-Cause Mortality Among Adults in Japan, China, Singapore, and Korea(American Medical Association, 2021-09-03) Svensson T; Saito E; Svensson AK; Melander O; Orho-Melander M; Mimura M; Rahman S; Sawada N; Koh W-P; Shu X-O; Tsuji I; Kanemura S; Park SK; Nagata C; Tsugane S; Cai H; Yuan J-M; Matsuyama S; Sugawara Y; Wada K; Yoo K-Y; Chia KS; Boffetta P; Ahsan H; Zheng W; Kang D; Potter JD; Inoue MIMPORTANCE: The association between long sleep duration and mortality appears stronger in East Asian populations than in North American or European populations. OBJECTIVES: To assess the sex-specific association between sleep duration and all-cause and major-cause mortality in a pooled longitudinal cohort and to stratify the association by age and body mass index. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of individual-level data from 9 cohorts in the Asia Cohort Consortium was performed from January 1, 1984, to December 31, 2002. The final population included participants from Japan, China, Singapore, and Korea. Mean (SD) follow-up time was 14.0 (5.0) years for men and 13.4 (5.3) years for women. Data analysis was performed from August 1, 2018, to May 31, 2021. EXPOSURES: Self-reported sleep duration, with 7 hours as the reference category. MAIN OUTCOMES AND MEASURES: Mortality, including deaths from all causes, cardiovascular disease, cancer, and other causes. Sex-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression with shared frailty models adjusted for age and the key self-reported covariates of marital status, body mass index, smoking status, alcohol consumption, physical activity, history of diabetes and hypertension, and menopausal status (for women). RESULTS: For 322 721 participants (mean [SD] age, 54.5 [9.2] years; 178 542 [55.3%] female), 19 419 deaths occurred among men (mean [SD] age of men, 53.6 [9.0] years) and 13 768 deaths among women (mean [SD] age of women, 55.3 [9.2] years). A sleep duration of 7 hours was the nadir for associations with all-cause, cardiovascular disease, and other-cause mortality in both men and women, whereas 8 hours was the mode sleep duration among men and the second most common sleep duration among women. The association between sleep duration and all-cause mortality was J-shaped for both men and women. The greatest association for all-cause mortality was with sleep durations of 10 hours or longer for both men (hazard ratio [HR], 1.34; 95% CI, 1.26-1.44) and women (HR, 1.48; 95% CI, 1.36-1.61). Sex was a significant modifier of the association between sleep duration and mortality from cardiovascular disease (χ25 = 13.47, P = .02), cancer (χ25 = 16.04, P = .007), and other causes (χ25 = 12.79, P = .03). Age was a significant modifier of the associations among men only (all-cause mortality: χ25 = 41.49, P < .001; cancer: χ25 = 27.94, P < .001; other-cause mortality: χ25 = 24.51, P < .001). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that sleep duration is a behavioral risk factor for mortality in both men and women. Age was a modifier of the association between sleep duration in men but not in women. Sleep duration recommendations in these populations may need to be considered in the context of sex and age.
- ItemFine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.(Springer Nature, 2024-04-26) Chen Z; Guo X; Tao R; Huyghe JR; Law PJ; Fernandez-Rozadilla C; Ping J; Jia G; Long J; Li C; Shen Q; Xie Y; Timofeeva MN; Thomas M; Schmit SL; Díez-Obrero V; Devall M; Moratalla-Navarro F; Fernandez-Tajes J; Palles C; Sherwood K; Briggs SEW; Svinti V; Donnelly K; Farrington SM; Blackmur J; Vaughan-Shaw PG; Shu X-O; Lu Y; Broderick P; Studd J; Harrison TA; Conti DV; Schumacher FR; Melas M; Rennert G; Obón-Santacana M; Martín-Sánchez V; Oh JH; Kim J; Jee SH; Jung KJ; Kweon S-S; Shin M-H; Shin A; Ahn Y-O; Kim D-H; Oze I; Wen W; Matsuo K; Matsuda K; Tanikawa C; Ren Z; Gao Y-T; Jia W-H; Hopper JL; Jenkins MA; Win AK; Pai RK; Figueiredo JC; Haile RW; Gallinger S; Woods MO; Newcomb PA; Duggan D; Cheadle JP; Kaplan R; Kerr R; Kerr D; Kirac I; Böhm J; Mecklin J-P; Jousilahti P; Knekt P; Aaltonen LA; Rissanen H; Pukkala E; Eriksson JG; Cajuso T; Hänninen U; Kondelin J; Palin K; Tanskanen T; Renkonen-Sinisalo L; Männistö S; Albanes D; Weinstein SJ; Ruiz-Narvaez E; Palmer JR; Buchanan DD; Platz EA; Visvanathan K; Ulrich CM; Siegel E; Brezina S; Gsur A; Campbell PT; Chang-Claude J; Hoffmeister M; Brenner H; Slattery ML; Potter JD; Tsilidis KK; Schulze MB; Gunter MJ; Murphy N; Castells A; Castellví-Bel S; Moreira L; Arndt V; Shcherbina A; Bishop DT; Giles GG; Southey MC; Idos GE; McDonnell KJ; Abu-Ful Z; Greenson JK; Shulman K; Lejbkowicz F; Offit K; Su Y-R; Steinfelder R; Keku TO; van Guelpen B; Hudson TJ; Hampel H; Pearlman R; Berndt SI; Hayes RB; Martinez ME; Thomas SS; Pharoah PDP; Larsson SC; Yen Y; Lenz H-J; White E; Li L; Doheny KF; Pugh E; Shelford T; Chan AT; Cruz-Correa M; Lindblom A; Hunter DJ; Joshi AD; Schafmayer C; Scacheri PC; Kundaje A; Schoen RE; Hampe J; Stadler ZK; Vodicka P; Vodickova L; Vymetalkova V; Edlund CK; Gauderman WJ; Shibata D; Toland A; Markowitz S; Kim A; Chanock SJ; van Duijnhoven F; Feskens EJM; Sakoda LC; Gago-Dominguez M; Wolk A; Pardini B; FitzGerald LM; Lee SC; Ogino S; Bien SA; Kooperberg C; Li CI; Lin Y; Prentice R; Qu C; Bézieau S; Yamaji T; Sawada N; Iwasaki M; Le Marchand L; Wu AH; Qu C; McNeil CE; Coetzee G; Hayward C; Deary IJ; Harris SE; Theodoratou E; Reid S; Walker M; Ooi LY; Lau KS; Zhao H; Hsu L; Cai Q; Dunlop MG; Gruber SB; Houlston RS; Moreno V; Casey G; Peters U; Tomlinson I; Zheng WGenome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
- ItemGenome-wide interaction analysis of folate for colorectal cancer risk.(Elsevier B.V., 2023-11) Bouras E; Kim AE; Lin Y; Morrison J; Du M; Albanes D; Barry EL; Baurley JW; Berndt SI; Bien SA; Bishop TD; Brenner H; Budiarto A; Burnett-Hartman A; Campbell PT; Carreras-Torres R; Casey G; Cenggoro TW; Chan AT; Chang-Claude J; Conti DV; Cotterchio M; Devall M; Diez-Obrero V; Dimou N; Drew DA; Figueiredo JC; Giles GG; Gruber SB; Gunter MJ; Harrison TA; Hidaka A; Hoffmeister M; Huyghe JR; Joshi AD; Kawaguchi ES; Keku TO; Kundaje A; Le Marchand L; Lewinger JP; Li L; Lynch BM; Mahesworo B; Männistö S; Moreno V; Murphy N; Newcomb PA; Obón-Santacana M; Ose J; Palmer JR; Papadimitriou N; Pardamean B; Pellatt AJ; Peoples AR; Platz EA; Potter JD; Qi L; Qu C; Rennert G; Ruiz-Narvaez E; Sakoda LC; Schmit SL; Shcherbina A; Stern MC; Su Y-R; Tangen CM; Thomas DC; Tian Y; Um CY; van Duijnhoven FJ; Van Guelpen B; Visvanathan K; Wang J; White E; Wolk A; Woods MO; Ulrich CM; Hsu L; Gauderman WJ; Peters U; Tsilidis KKBackground Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate’s role in CRC. Objectives Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. Methods We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). Results Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. Conclusions Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.
- ItemHuman papillomavirus self-testing among unscreened and under-screened Māori, Pasifika and Asian women in Aotearoa New Zealand: A preference survey among responders and interviews with clinical-trial nonresponders(John Wiley and Sons Ltd, 2022-12) Sherman SM; Brewer N; Bartholomew K; Bromhead C; Crengle S; Cunningham C; Douwes J; Foliaki S; Grant J; Maxwell A; McPherson G; Scott N; Wihongi H; Potter JDINTRODUCTION: Māori, Pasifika and Asian women are less likely to attend cervical screening and Māori and Pasifika women are more likely to be diagnosed with later-stage cervical cancer than other women in Aotearoa New Zealand. This study-with under-screened women taking part in a randomized-controlled trial comparing self-testing and standard screening-explored the acceptability of a human papillomavirus (HPV) self-test kit and the preferred method for receiving it. METHODS: Māori, Pasifika and Asian women (N= 376) completed a cross-sectional postal questionnaire. Twenty-six women who had not accepted the trial invitation were interviewed to understand their reasons for nonparticipation. RESULTS: Most women found the self-test kit easy and convenient to use and reported that they did not find it painful, uncomfortable or embarrassing. This was reflected in the preference for a self-test over a future smear test on the same grounds. Most women preferred to receive the kit by mail and take the test themselves, rather than having it done by a doctor or nurse. There was a range of preferences relating to how to return the kit. Phone calls with nonresponders revealed that, although most had received the test kit, the reasons for not choosing to be involved included not wanting to, being too busy or forgetting. CONCLUSION: HPV self-testing was acceptable for Māori, Pasifika and Asian women in Aotearoa New Zealand. HPV self-testing has considerable potential to reduce the inequities in the current screening programme and should be made available with appropriate delivery options as soon as possible. PATIENT OR PUBLIC CONTRIBUTION: This study explored the acceptability of HPV self-testing and their preferences for engaging with it among Māori, Pasifika and Asian women. Thus, women from these underserved communities were the participants and focus of this study.
- ItemIdentifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures(Springer Nature Limited, 2022-06-06) Georgeson P; Harrison TA; Pope BJ; Zaidi SH; Qu C; Steinfelder RS; Lin Y; Joo JE; Mahmood K; Clendenning M; Walker R; Amitay EL; Berndt SI; Brenner H; Campbell PT; Cao Y; Chan AT; Chang-Claude J; Doheny KF; Drew DA; Figueiredo JC; French AJ; Gallinger S; Giannakis M; Giles GG; Gsur A; Gunter MJ; Hoffmeister M; Hsu L; Huang W-Y; Limburg P; Manson JE; Moreno V; Nassir R; Nowak JA; Obón-Santacana M; Ogino S; Phipps AI; Potter JD; Schoen RE; Sun W; Toland AE; Trinh QM; Ugai T; Macrae FA; Rosty C; Hudson TJ; Jenkins MA; Thibodeau SN; Winship IM; Peters U; Buchanan DDCarriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers (p = 2 × 10-23 and p = 6 × 10-11, respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers.
- ItemPasifika women's knowledge and perceptions of cervical-cancer screening and the implementation of self-testing in Aotearoa New Zealand: A qualitative study(Elsevier Ltd, 2022-11) Brewer N; Foliaki S; Gray M; Potter JD; Douwes JBACKGROUND: In Aotearoa New Zealand, Pasifika women have a higher rate of cervical cancer incidence and mortality than European/Other women and a lower screening rate. Despite actions to reduce the barriers, there has been little change in screening coverage for Pasifika women since 2007. Novel strategies are therefore required. Persistent cervical infection with oncogenic human papillomavirus (HPV) causes virtually all cervical cancers and HPV testing will be implemented in Aotearoa in 2023, with women being able to choose to self-test. We undertook a qualitative focus group (FG) study with Pasifika women to explore their perspectives on the barriers to, and facilitators of, HPV self-testing and how best to implement this in Aotearoa. METHODS: A trained female Pasifika Research Assistant facilitated participant recruitment and the FGs. Eligible participants self-identified as Pasifika, were aged 30-69 years, in the Wellington area, who had never been screened or who were overdue (≥5 years) for cervical-cancer screening. Recruitment was predominantly through Pasifika key-informant networks and in collaboration with Pasifika primary care providers. Participants were offered face-to-face FGs but, due to occasional Covid-19 restrictions and personal preferences, FGs via Zoom were also used. The FGs were audio-recorded and transcribed verbatim. The FG transcripts were thematically analysed. FINDINGS: Seven FGs were conducted with 24 participants. We identified five main themes around barriers and potential facilitators of HPV self-testing in Pasifika women: 1) perceptions and knowledge of cervical-cancer screening; 2) challenges to engaging in organised cervical screening; 3) perceptions of self-testing for HPV and challenges women face when deciding to self-test; 4) enthusiasm for an HPV self-test; and 5) information and communication. Knowledge about cervical cancer and screening varied considerably among participants, with some never having heard about cervical-cancer screening. The main challenges that were raised were personal privacy and confidentiality and time management. There was consensus around the need for adequate, consistent, and accurate accessible information to boost the confidence of women undertaking self-testing. In general, the participants were eager for self-testing to be made available soon. This was accompanied by the need for the promotion and implementation of self-testing to include a collective/community approach consistent with Pasifika worldviews. INTERPRETATION: Although participants were enthusiastic about HPV self-testing, multi-level and interacting barriers exist to participation by Pasifika women in HPV self-testing. Implementation of self-testing in Aotearoa New Zealand should be accompanied by clear information about the entire process, using culturally appropriate tailored educational campaigns in different Pasifika languages. FUNDING: The study was supported by the Collaboration for Cancer Research Aotearoa New Zealand (CCR).
- ItemProspective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer.(BioMed Central, 2023-10-13) Nimptsch K; Aleksandrova K; Pham TT; Papadimitriou N; Janke J; Christakoudi S; Heath A; Olsen A; Tjønneland A; Schulze MB; Katzke V; Kaaks R; van Guelpen B; Harbs J; Palli D; Macciotta A; Pasanisi F; Yohar SMC; Guevara M; Amiano P; Grioni S; Jakszyn PG; Figueiredo JC; Samadder NJ; Li CI; Moreno V; Potter JD; Schoen RE; Um CY; Weiderpass E; Jenab M; Gunter MJ; Pischon TBACKGROUND: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach. METHODS: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. RESULTS: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37). CONCLUSIONS: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.