Increased risk of colorectal cancer in patients diagnosed with breast cancer in women

Lu, Yunxia; Segelman, Josefin; Nordgren, Ann; Lindström, Lars; Frisell, Jan; Martling, Anna

doi:10.1016/j.canep.2016.01.006

Cited by 21 publications

(15 citation statements)

References 30 publications

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“…A recent study found that women diagnosed with breast cancer have a 1.59-fold (95% Confidence Interval (CI): 1.53-1.65) increased risk of developing colorectal cancer compared to the general population (37). …”

Section: Discussionmentioning

confidence: 99%

Quantifying the Genetic Correlation between Multiple Cancer Types

Lindström

Finucane

Bulik-Sullivan

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Many cancers share specific genetic risk factors including both rare high-penetrance mutations and common single nucleotide polymorphisms (SNPs) identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies. In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 non-cancer diseases and traits. After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (p<0.003) genetic correlations between pancreatic and colorectal cancer (rg=0.55, p=0.003), lung and colorectal cancer (rg=0.31, p=0.001). We also found suggestive genetic correlations between lung and breast cancer (rg=0.27, p=0.009), and colorectal and breast cancer (rg=0.22, p=0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected p-value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg=0.41, p=1.03x10-6). We also observed nominally significant genetic correlations between body mass index (BMI) and all cancers except ovarian cancer. Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.

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Section: Discussionmentioning

confidence: 99%

Quantifying the Genetic Correlation between Multiple Cancer Types

Lindström

Finucane

Bulik-Sullivan

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In contrast, other studies have suggested the greater endogenous plasma estrone (E 1 ) concentrations in postmenopausal women increase CRC risk ( 5 ). Similarly, women with estrogen-dependent breast cancer have a greater risk of developing CRC ( 6 ). Women taking HRT at the time of the diagnosis of CRC are more likely to present with advanced-stage disease ( 7 ), suggesting that either the symptoms associated with HRT use leads to a delayed clinical diagnosis or that HRT increases CRC development and proliferative rates.…”

mentioning

confidence: 99%

Estrogen Activation by Steroid Sulfatase Increases Colorectal Cancer Proliferation via GPER

Gilligan

Rahman

Hewitt

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:Estrogens affect the incidence and progression of colorectal cancer (CRC), although the precise molecular mechanisms remain ill-defined.Objective:The present study investigated prereceptor estrogen metabolism through steroid sulphatase (STS) and 17β-hydroxysteroid dehydrogenase activity and subsequent nongenomic estrogen signaling in human CRC tissue, in The Cancer Genome Atlas colon adenocarcinoma data set, and in in vitro and in vivo CRC models. We aimed to define and therapeutically target pathways through which estrogens alter CRC proliferation and progression.Design, Setting, Patients, and Interventions:Human CRC samples with normal tissue-matched controls were collected from postmenopausal female and age-matched male patients. Estrogen metabolism enzymes and nongenomic downstream signaling pathways were determined. CRC cell lines were transfected with STS and cultured for in vitro and in vivo analysis. Estrogen metabolism was determined using an ultra-performance liquid chromatography–tandem mass spectrometry method.Primary Outcome Measure:The proliferative effects of estrogen metabolism were evaluated using 5-bromo-2′-deoxyuridine assays and CRC mouse xenograft studies.Results:Human CRC exhibits dysregulated estrogen metabolism, favoring estradiol synthesis. The activity of STS, the fundamental enzyme that activates conjugated estrogens, is significantly (P < 0.001) elevated in human CRC compared with matched controls. STS overexpression accelerates CRC proliferation in in vitro and in vivo models, with STS inhibition an effective treatment. We defined a G-protein–coupled estrogen receptor (GPER) proproliferative pathway potentially through increased expression of connective tissue growth factor in CRC.Conclusion:Human CRC favors estradiol synthesis to augment proliferation via GPER stimulation. Further research is required regarding whether estrogen replacement therapy should be used with caution in patients at high risk of developing CRC.

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“…Associations between CRC and breast, ovarian, and uterine cancers have been reported in previous studies [31][32][33][34][35]. Hormonal influences have been suggested to explain these observed associations, though it is not evident whether these hormonal influences act similarly in the context of CRC as they do in the development of breast, ovarian, and uterine cancers [36][37][38].…”

Section: Discussionmentioning

confidence: 93%

Patients with non-colorectal cancers may be at elevated risk of colorectal neoplasia

et al. 2020

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Background: Screening for colonic neoplasia has decreased the incidence of colorectal cancer in the United States in the past two decades. Whether personal history of noncolorectal cancer is a risk factor for colonic neoplasia has not been well studied. We assessed the risk of colorectal neoplasia in noncolorectal cancer survivors. Methods: We conducted a retrospective study of patients who had undergone colonoscopy for any indication between 2009 and 2018. Colonic adenoma detection rate and multivariate logistic regression were conducted to assess for the primary outcomes of the study. Results: The study included 9408 cancer patients and 3295 control patients. Colonic adenomas were detected in 4503 cancer patients (48%) and 950 cancer-free patients (29%). Histologic examination of these adenomas revealed tubulovillous features in 620 patients (5%) and villous in 153 (1%). High-grade dysplasia was detected in 1611 patients (13%). Invasive colorectal adenocarcinoma was detected in 455 patients (12%); this rate was highest in patients with multiple myeloma (14%). Multivariate analysis revealed that a personal history of noncolorectal cancer was associated with increased risk of adenoma (Odd ratio, 2.04; 95% CI, 1.84-2.26; P<0.001). The adenoma detection rate was 30% in patients younger than 40 years (n=1211), 32% in patients between 41 and 50 years (n=812), 47% in patients between 51 and 60 years (n=2892), and 55% in patients older than 60 years (n=4493). Conclusions: The adenoma detection rate in patients with a personal history of noncolorectal cancer is higher than the reported rate of the general population and our control group.

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Increased risk of colorectal cancer in patients diagnosed with breast cancer in women

Cited by 21 publications

References 30 publications

Quantifying the Genetic Correlation between Multiple Cancer Types

Quantifying the Genetic Correlation between Multiple Cancer Types

Estrogen Activation by Steroid Sulfatase Increases Colorectal Cancer Proliferation via GPER

Patients with non-colorectal cancers may be at elevated risk of colorectal neoplasia

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