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The relationship between gravidity and parity and colorectal cancer risk.

ABSTRACT: The influence of hormonal changes caused by pregnancy has been well studied in relation to colorectal cancer risk, but the association remains undefined. The purpose of this investigation was to examine in a case-control study the relationship between differences in gravidity and parity and colorectal cancer risk and if the association varied by microsatellite instability (MSI), a feature more common in women.The study population included incident colorectal cancer patients (n = 1014), aged 50-74 years, diagnosed in 1998-2002 in Washington state and controls (n = 1064) randomly selected from population lists. All study subjects completed telephone interviews to ascertain prior pregnancies, live births, and other covariates. Case tissue samples were obtained for MSI analyses. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, family history of colorectal cancer, body mass index (BMI), education, endoscopy screening, oral contraceptive use, hormone therapy use, smoking, and alcohol consumption.There was an approximate 30%-50% reduction in risk of colon cancer associated with gravidity, which was attenuated in the analysis with parity. Increasing gravidity and parity were associated with a suggestion of a decreasing trend in risk for rectal cancer (p for trend = 0.07). Compared with women who had equal numbers of pregnancies and live births, women who were nulligravid and nulliparous had a 40%-60% increased risk of colon cancer. There was a suggestion of a reduced risk of both colon and rectal cancer associated with one more pregnancy than live birth. There was a suggestion of an increased risk of MSI-high tumors with nulligravidity and nulliparity.These results confirm the importance of pregnancy events in the etiology of colon and rectal cancer.

SUBMITTER: Wernli KJ

PROVIDER: S-EPMC2851134 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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The relationship between gravidity and parity and colorectal cancer risk.

Wernli Karen J KJ Wang Yinghui Y Zheng Yingye Y Potter John D JD Newcomb Polly A PA

Journal of women's health (2002) 20090701 7

<h4>Objectives</h4>The influence of hormonal changes caused by pregnancy has been well studied in relation to colorectal cancer risk, but the association remains undefined. The purpose of this investigation was to examine in a case-control study the relationship between differences in gravidity and parity and colorectal cancer risk and if the association varied by microsatellite instability (MSI), a feature more common in women.<h4>Methods</h4>The study population included incident colorectal ca ...[more]

PMID: 19575687

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Project description:ObjectivesDespite a hypothesised connection of reproductive history with hypertension and mortality, the nature of this association is poorly characterised. We evaluated the association of parity and gravidity with blood pressure, hypertension and all-cause mortality.DesignProspective cohort study.SettingHealth Effects of Arsenic Longitudinal Study cohort in rural Bangladesh.ParticipantsThere were 21 634 Bangladeshi women recruited in 2000-2002, 2006-2008 and 2010-2014 included in the present analysis.MethodsReproductive history was ascertained through an interviewer-administered questionnaire at the baseline visit. Blood pressure was measured by a trained study physician following a standard protocol at the baseline visit. Vital status was ascertained at the biennial follow-up of study participants through June 2017. Linear and logistic regression models estimated the relationship between parity and gravidity with blood pressure and hypertension, respectively. Cox proportional hazards models estimated the relationship with all-cause mortality only among women aged >45 years.ResultsDiastolic blood pressure was lowest in women with parity one (reference) and elevated in nulliparous women (adjusted % change=3.12; 95% CI 1.93 to 4.33) and women with parity >2 (adjusted % change=1.71; 95% CI 1.12 to 2.31). The associations with nulliparity were stronger for women aged >45 years. Similar association patterns were observed with hypertension. Further, in nulliparous women aged >45 years, 265 deaths (6.6%) were ascertained during the follow-up period (median follow-up time=8 years), and we observed suggestive elevated risks of all-cause mortality (adjusted HR 3.83; 95% CI 0.74 to 19.78). The relationships between reproductive history, blood pressure, hypertension and mortality were similar when modelling reproductive history as gravidity rather than parity.ConclusionsFor women in rural Bangladesh, nulliparity and nulligravidity appear to be associated with higher blood pressure and subsequent elevated risk of mortality.

Project description:BackgroundMicrosomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.MethodsTwo investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.ResultsThis meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83-0.98; dominant model, OR = 0.92, 95%CI = 0.85-0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies' publication time, the results were persistent and robust.ConclusionThis meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.

Project description:Background Malaria infection during pregnancy can cause significant morbidity and mortality to a pregnant woman, her fetus and newborn. In areas of high endemic transmission, gravidity is an important risk factor for infection, but there is a complex relationship with other exposure-related factors, and use of protective measures. This study investigated the association between gravidity and placental malaria (PM), among pregnant women aged 14–49 in Kintampo, a high transmission area of Ghana. Methods Between 2008 and 2011, as part of a study investigating the association between PM and malaria in infancy, pregnant women attending antenatal care (ANC) clinics in the study area were enrolled and followed up until delivery. The outcome of PM was assessed at delivery by placental histopathology. Multivariable logistic regression analyses were used to investigate the association between gravidity and PM, identify other key risk factors, and control for potential confounders. Pre-specified effect modifiers including area of residence, socio-economic score (SES), ITN use and IPTp-SP use were explored. Results The prevalence of PM was 65.9% in primigravidae, and 26.5% in multigravidae. After adjusting for age, SES and relationship status, primigravidae were shown to have over three times the odds of PM compared to multigravidae, defined as women with 2 or more previous pregnancies [adjusted OR = 3.36 (95% CI 2.39–4.71), N = 1808, P < 0.001]. The association appeared stronger in rural areas [OR for PG vs. MG was 3.79 (95% CI 3.61–5.51) in rural areas; 2.09 (95% CI 1.17–3.71) in urban areas; P for interaction = 0.07], and among women with lower socio-economic scores [OR for PG vs. MG was 4.73 (95% CI 3.08–7.25) amongst women with lower SES; OR = 2.14 (95% CI 1.38–3.35) among women with higher SES; P for interaction = 0.008]. There was also evidence of lower risk among primigravidae with better use of the current preventive measures IPTp and LLIN. Conclusions The burden of PM is most heavily focused on primigravidae of low SES living in rural areas of high transmission. Programmes should prioritize primigravidae and young women of child-bearing age for interventions such as LLIN distribution, educational initiatives and treatment to reduce the burden of malaria in first pregnancy. Supplementary Information The online version contains supplementary material available at 10.1186/s12936-022-04252-0.

Project description:BackgroundFucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-ß-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC.MethodsIn this study, we first examined the expression of fucosylated proteins in 50 cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided.ResultsWe found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P≤ .02). L-fucose uptake assay revealed that L-fucose incorporation, as well as fucosylated protein release, was high in cells rich in fucosylated proteins. L-fucose-bound liposomes effectively delivered Cy5.5 into CRC cells. The excess of L-fucose decreased the efficiency of Cy5.5 uptake through L-fucose-bound liposomes, suggesting an L-fucose receptor dependency. Intravenously injected, L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition (relative tumor growth ratio: no treatment group [NT], 8.29 ± 3.09; SN38-treated group [SN38], 3.53 ± 1.47; liposome-carrying, SN38-treated group [F0], 3.1 ± 1.39; L-fucose-bound, liposome-carrying, SN38-treated group [F50], 0.94 ± 0.89; F50 vs NT,P= .003; F50 vs SN38,P= .02, F50 vs F0,P= .04), as well as prolonging survival of mouse xenograft models (log-rank test,P< .001).ConclusionsThus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.

Dataset Information

The relationship between gravidity and parity and colorectal cancer risk.

Publications

The relationship between gravidity and parity and colorectal cancer risk.

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