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Association of Non-Steroidal Anti-Inflammatory Drugs, Genetic Risk, and Environmental Risk Factors with Incidence of Colorectal Cancer.

ABSTRACT: Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with the lower risk of colorectal cancer (CRC). However, whether regular use of NSAIDs could attenuate the effect of genetic risk and environmental risk factors on CRC is unknown. We aimed to evaluate the association of NSAID use, genetic risk, and environmental risk factors with CRC. Using data from a UK Biobank, a Cox proportional hazards model was performed to estimate the risk of CRC according to NSAID use, polygenic risk score, and environmental risk factors. Regular use of NSAIDs was associated with a 36.0% lower risk of CRC. No statistically significant interaction was observed between NSAID use and the genetic risk score (p = 0.190), and between NSAID use and the environmental risk score (p = 0.740). However, regular NSAID use was still associated with lower CRC incidence among subjects with either high environmental risk or high genetic risk. Furthermore, the genetic and environmental risk of CRC were additives. These findings appear to support the chemopreventive effect of regular NSAID use. Furthermore, controlling of modifiable environmental risk factors can reduce the CRC risk, especially among individuals with a moderate or high genetic risk of CRC.

SUBMITTER: Ren J

PROVIDER: S-EPMC9600467 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Association of Non-Steroidal Anti-Inflammatory Drugs, Genetic Risk, and Environmental Risk Factors with Incidence of Colorectal Cancer.

Ren Jiaojiao J Zhang Peidong P Li Zhihao Z Zhang Xiru X Zhong Wenfang W Song Weiqi W Wang Xing X Gao Pingming P Mao Chen C

Cancers 20221020 20

Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with the lower risk of colorectal cancer (CRC). However, whether regular use of NSAIDs could attenuate the effect of genetic risk and environmental risk factors on CRC is unknown. We aimed to evaluate the association of NSAID use, genetic risk, and environmental risk factors with CRC. Using data from a UK Biobank, a Cox proportional hazards model was performed to estimate the risk of CRC according to NSAID use, polygeni ...[more]

PMID: 36291921

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Project description:BackgroundHeavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.ObjectivesTo determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB.Search methodsWe searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles.Selection criteriaThe inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB.Data collection and analysisWe identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis.Main resultsAs a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision.Authors' conclusionsNSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.

Dataset Information

Association of Non-Steroidal Anti-Inflammatory Drugs, Genetic Risk, and Environmental Risk Factors with Incidence of Colorectal Cancer.

Publications

Association of Non-Steroidal Anti-Inflammatory Drugs, Genetic Risk, and Environmental Risk Factors with Incidence of Colorectal Cancer.

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