Sexual Dimorphism in Colon Cancer

Abancens, Maria; Bustos, Viviana; Harvey, Harry; McBryan, Jean; Harvey, Brian

doi:10.3389/fonc.2020.607909

Cited by 125 publications

(138 citation statements)

References 292 publications

(314 reference statements)

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“…6 However, because there are potential sex-based differences in nutrient metabolism 7 and CRC risk, 8 a study leveraging a more diverse population is needed to confirm these findings. Cohort studies 9,10 and reviews 8,11 have reported that, compared with men, women have a lower overall incidence of CRC but a higher risk of proximal colon cancer, which tends to be more advanced and less differentiated than distal colon cancer. 8,10,12 In addition, there are potential sex differences in the gut microbiome in response to diet.…”

Section: Introductionmentioning

confidence: 99%

Association Between the Sulfur Microbial Diet and Risk of Colorectal Cancer

et al. 2021

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IMPORTANCE Sulfur-metabolizing bacteria that reduce dietary sulfur to hydrogen sulfide have been associated with colorectal cancer (CRC). However, there are limited studies investigating the association between diet and sulfur-metabolizing bacteria in the development of CRC. OBJECTIVETo develop a dietary score that correlates with gut sulfur-metabolizing bacteria and to examine its association with CRC risk.

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Section: Introductionmentioning

confidence: 99%

Association Between the Sulfur Microbial Diet and Risk of Colorectal Cancer

et al. 2021

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“…For both gastric and esophageal adenocarcinomas, behavioral risk factors, such as obesity or exposure to carcinogens like tobacco smoking, do not entirely explain the sex disparity in incidence seen across multiple populations [3][4][5], thus strongly suggesting sex differences in susceptibility and/or biology for this type of cancer. In fact, increasing evidence suggests a sexual dimorphism in cancer biology, and sex-biased molecular signatures have been observed across multiple tumor types [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in tumor characteristics, treatment, and outcomes of gastric and esophageal cancer surgery: nationwide cohort data from the Dutch Upper GI Cancer Audit

et al. 2021

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Background Sex differences in clinicopathological characteristics, treatment, and postoperative outcomes of gastric and esophageal cancer are largely undefined. This study aimed to compare tumor and treatment characteristics and outcomes of gastric and esophageal cancer surgery between male and female patients. Methods Patients after elective surgery for primary esophageal (EAC) or gastric adenocarcinoma (GAC) registered in the Dutch Upper GI Cancer Audit between 2011 and 2016 were included. The primary endpoint, 5-year relative survival with relative excess risk (RER), i.e., adjusted for the normal life expectancy, was compared between male and female patients with EAC and GAC. Results In total, 4937 patients were included (75% male) with a mean age of 66 years. cT and cN-stages showed a similar distribution in male and female patients. In females, antrum GAC was more frequent (47% vs. 38%, p < 0.001). Female patients with EAC less frequently received neo-adjuvant treatment (OR = 0.60, 95% CI 0.38–0.96, p = 0.033). For GAC, less postoperative morbidity (33% vs. 38% p = 0.017) and less re-interventions (12% vs. 16%, p = 0.008) were observed in females, although they had inferior 5-year relative survival (49% vs. 56%, RER = 1.31, 95% CI 1.09–1.58, p = 0.004). No differences in relative survival of EAC were observed. Conclusions In addition to significant sex differences in tumor location, female patients with esophageal adenocarcinoma less frequently received neo-adjuvant therapy, and female patients with gastric adenocarcinoma had inferior relative survival. Further consideration and exploration of sex differences in surgical treatment and outcomes are necessary to improve tailored treatment and outcomes.

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“…Our previous study identified that multiple LysoPCs and LysoPEs were upregulated in female patients with RCC (stage I) only, suggesting that the higher level of lysophospholipids in women with RCC would promote fatty acid supply that is essential for cancer cell growth at early stages 21 . It has also been discussed that sex-specific estrogen regulation may inhibit CRC cell survival by suppressed triglyceride biosynthesis, a vital lipid marker related to CRC progression 17 .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, sex-related differences in CRC prognosis have become increasingly important in cancer research 16,17 . Female patients have a higher prevalence of right-sided colon cancer (RCC), which is associated with poorer overall survival (OS) 18,19 .…”

Section: Introductionmentioning

confidence: 99%

Asparagine metabolism in tumors is linked to poor survival in females with colorectal cancer: A cohort study

Shen

Cai

Lü

et al. 2021

Preprint

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Background or PurposeThe interplay between the sex-specific differences in tumor metabolome and colorectal cancer (CRC) prognosis has never been studied and represents an opportunity to improve patient outcomes. This study aims to examine the link between tumor metabolome and prognosis by sex for CRC patients.MethodsUsing untargeted metabolomics analysis, abundances of 91 metabolites were obtained from primary tumor tissues from 197 patients (N=95 females, N=102 males) after surgical colectomy for stage I-III CRC. Cox Proportional Hazards (PH) regression models were applied to estimate the associations between tumor metabolome and 5-year overall survival (OS) and 5-year recurrence-free survival (RFS), and their interactions with sex.ResultsEleven metabolites had significant sex differences in their associations with 5-year OS, and five metabolites for 5-year RFS (Pinteraction < .05). The metabolites asparagine and serine had sex interactions for both OS and RFS. Furthermore, sex-specific differences were found in the associations between prognosis and metabolic pathways. Notably, in the asparagine synthetase (ASNS)-catalyzed asparagine synthesis pathway, asparagine was associated with substantially poorer OS (hazard ratio [HR] = 6.39, 95% confidence interval [CI] = 1.78-22.91, P = .004) and RFS (HR = 4.36, 95% CI = 1.39-13.68, P = .01) for female patients only (Pinteraction, OS = .02, Pinteraction, RFS = .003). Similar prognostic disadvantages in females were seen in lysophospholipid and polyamine synthesis.Discussion or ConclusionsUnique metabolite profiles indicated increased asparagine synthesis was associated with poorer prognosis for females only, providing insights into precision medicine for CRC treatment stratified by sex.

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Sexual Dimorphism in Colon Cancer

Cited by 125 publications

References 292 publications

Association Between the Sulfur Microbial Diet and Risk of Colorectal Cancer

Association Between the Sulfur Microbial Diet and Risk of Colorectal Cancer

Sex differences in tumor characteristics, treatment, and outcomes of gastric and esophageal cancer surgery: nationwide cohort data from the Dutch Upper GI Cancer Audit

Asparagine metabolism in tumors is linked to poor survival in females with colorectal cancer: A cohort study

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