Sex-Specific Association between Family History of Diabetes and Risk of Colorectal Cancer: Two Prospective Cohort Studies

Ma, Wenjie; Song, Mingyang; Kværner, Ane Sørlie; Prescott, Jennifer; Chan, Andrew T.; Giovannucci, Edward; Zhang, Xuehong

doi:10.1158/1940-6207.capr-18-0159

Cited by 9 publications

(12 citation statements)

References 40 publications

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“…Bauer et al 39 investigated familial aggregation of diabetes and colorectal neoplasia, and found positive associations between familial diabetes and adenomatous polyps or CRC. Ma et al 17 reported in 2018 that family history of diabetes is associated with risk of CRC in a sex-specific manner, and that the relationship is more pronounced in patients under 60 years, and only significant in males. We found this feature in both sexes with YOCRC, however, the numbers were low and hence it is not possible to confirm this observation.…”

Section: Resultsmentioning

confidence: 99%

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Young‐onset colorectal cancer is associated with a personal history of type 2 diabetes

Mikaeel

Symonds

Kimber

et al. 2020

Asia-Pac J Clncl Oncology

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Background Colorectal cancer (CRC) is rising in incidence in young adults, and this observation is currently unexplained. We investigated whether having a personal history of type 2 diabetes mellitus (T2D) was a potential risk factor for young‐onset colorectal cancer (YOCRC). Methods The South Australian Young Onset (SAYO) CRC study is a series of young adults with CRC below age 55. Ninety unrelated YOCRC cases were recruited to the study. Personal history and detailed family history of T2D were obtained at face‐to‐face interview and confirmed from medical records. Whole exome sequencing was conducted on germline DNA from each CRC case. Controls for personal history studies of T2D were 240 patients with proven clear colonoscopies and no known CRC predispositions. Results The median age of YOCRC cases was 44 years (18–54) and of controls was 45 years (18–54), and 53% of both cases and controls were females (P = 0.99). Left‐sided (distal) CRC was seen in 67/89 (75%) of cases. A personal history of T2D was confirmed in 17/90 (19%) YOCRC patients compared with controls (12/240, 5%; P < 0.001; odds ratio = 4.4; 95% confidence interval, 2.0–9.7). YOCRC patients frequently reported at least one first‐degree relative with T2D (32/85, 38%). Ten of 87 (12%) of YOCRC cases had CRC‐related pathogenic germline variants, however, no pathogenic variants in familial diabetes‐associated genes were seen. Conclusions Though the mechanism remains unclear, our observations suggest that there is enrichment for personal history of T2D in YOCRC patients. Impact A diagnosis of T2D could therefore potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate.

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Section: Resultsmentioning

confidence: 99%

“…Although the link between CRC and T2D has been frequently reported in studies, 16 the association between personal and/or family history of T2D and YOCRC has not been widely investigated. 17 The aim of this study was to investigate whether personal history T2D was associated with YOCRC.…”

Section: Introductionmentioning

confidence: 99%

Young‐onset colorectal cancer is associated with a personal history of type 2 diabetes

Mikaeel

Symonds

Kimber

et al. 2020

Asia-Pac J Clncl Oncology

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“…Other studies obtained, however, opposite conclusions, with low leptin levels in patients with CRC [9–13], whereas certain investigators did not observe significant CRC-related changes of leptin [4,14] or adiponectin [17,18]. This discordance may be caused by different localizations of CRC in study-enrolled patients [18,19,21,22], by cancer staging [8,11,14] and multicenter approach [19–23].…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore unclear whether modifications in adipokine levels described in patients with digestive cancer represent a causative link or are merely an adaptive epiphenomenon [20]. Finally, the contrasting data described in the literature may be caused by the heterogeneity of studied groups with respect to tumor localization [3,9, 21,22], gender [7,23], weight modification [3,9], disease severity [8], chemotherapy [24] or due to statistical complexity caused by multicentricity of the study or complex metaanalysis [3,4,18,21,22]. In order to avoid these variations, one needs to choose a more homogenous series, in a single location at similar stages.…”

Section: Introductionmentioning

confidence: 99%

Leptin and adiponectin dynamics at patients with rectal neoplasm - Gender differences

et al. 2019

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Background Numerous studies associate adipokines with colorectal malignancy, but few data deal with patients suffering exclusively of rectal carcinoma (RC). Aims We evaluated leptin and adiponectin levels in RC patients compared to healthy population and their dynamics after surgery. Material and methods Serum leptin and adiponectin were evaluated before surgery in 59 RC consecutive patients (38 males and 21 females), and in age and weight matched healthy controls. Measurements were repeated at 24, 72 hours and 7 days after surgery. Results Adipokine levels were higher in women. Controls had higher leptin (32.±4.34 vs 9.51±1.73 ng/ml in women and 11±2.66 vs 2.54±0.39 ng/ml in men, p = 0.00048 and 0.0032) and lower adiponectin (9±0.64 vs 11.85±1.02 μg/ml in women and 7.39±0.51 vs 8.5±0.62 μg/ml in men, p = 0.017 and 0.019) than RC patients. Surgery caused an increase of leptin from 5.11±0.8 to 18.7±2.42 ng/ml, p = 6.85 x 10¨ 8 , and a decrease of adiponectin from 9.71±0.58 to 7.87±0.47 μg/ml, p = 1.4 x 10¨ 10 for all RC patients and returned thereafter to the initial range at 7 days. Adipokines were correlated with body weight (BW). The significance of correlation persisted after surgery only in males, but disappeared in females. Adipokines were not modified by tumor position, presurgical chemoradiotherapy or surgical technique. Women with RC experiencing weight loss had higher adiponectin than women without weight modifications (p<0.05 at all time points). Conclusions Adipokine levels of patients with RC differ from the healthy population, possibly reflecting an adaptation to disease. Adipokine modifications after surgery may be related to acute surgical stress. Whether leptin and adiponectin directly interact is not clear. Women have higher adipokine levels, more so after significant weight loss, but the strength of their correlation with BW decreases after surgery. These data suggest gender differences in the adipokine profile of RC patients which may find clinical applications.

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“… 6 A previous study suggested that patients with an FHD tended to have a higher risk of colorectal cancer (men, HR=1.19, 95% CI 1.04 to 1.36; women, HR=1.06, 95% CI 0.96 to 1.17) than those without an FHD. 5 Moreover, an FHD also plays an important role in the prevalence of pre-diabetes, 7 diabetes risk, 8 glycaemic control, 9 and insulin secretion and sensitivity. 10 A multicentre study that included 8106 participants without diabetes revealed that an important risk factor for pre-diabetes (OR=1.26, 95% CI 1.14 to 1.40) was an FHD, even after adjustments for potential confounders.…”

Section: Introductionmentioning

confidence: 99%

Effects of family history of diabetes on pancreatic β-cell function and diabetic ketoacidosis in newly diagnosed patients with type 2 diabetes: a cross-sectional study in China

et al. 2021

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ObjectiveTo investigate the association between a parental and/or sibling history of diabetes and clinical characteristics.DesignA cross-sectional study.SettingThe data were collected from the endocrinology department of The Second Xiangya Hospital of Central South University from June 2017 to October 2019.ParticipantsA total of 894 newly diagnosed patients with type 2 diabetes were recruited. Data on clinical characteristics were collected from patient medical records. Pancreatic β-cell function and insulin resistance were calculated with the homeostatic model assessment. SPSS V.25.0 was used to perform the analysis.ResultsThe percentages of patients with parental and sibling histories of diabetes were 14.8% and 9.8%, respectively. The prevalence of diabetic ketoacidosis (DKA) was 3.9%. Compared with those with no parental history of diabetes, patients with a parental history of diabetes were characterised by early-onset disease (41.70±10.88 vs 51.17±14.09 years), poor glycaemic control of fasting blood glucose (10.84±5.21 vs 8.91±4.38 mmol/L) and a high prevalence of DKA (7.6% vs 3.3%). The patients with a sibling history of diabetes had later disease onset (56.05±9.86 vs 49.09±14.29 years) and lower BMI (24.49±3.48 vs 25.69±3.86 kg/m2) than those with no sibling history of diabetes. Univariate regression suggested that both parental history (p=0.037) and sibling history (p=0.011) of diabetes were associated with β-cell function; however, multiple regression analysis showed that only a sibling history of diabetes was associated with β-cell function (p=0.038). Univariate regression revealed a positive correlation between parental history of diabetes (p=0.023, OR=2.416, 95% CI 1.132 to 5.156) and DKA. Unfortunately, this correlation was not statistically significant for either patients with a parental history (p=0.234, OR=1.646, 95% CI 0.724 to 3.743) or those with a sibling history (p=0.104, OR=2.319, 95% CI 0.841 to 6.389) after adjustments for confounders.ConclusionA sibling history of diabetes was associated with poor β-cell function, and a parental history of diabetes was associated with poor glycaemic control and a high prevalence of DKA.

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Sex-Specific Association between Family History of Diabetes and Risk of Colorectal Cancer: Two Prospective Cohort Studies

Cited by 9 publications

References 40 publications

Young‐onset colorectal cancer is associated with a personal history of type 2 diabetes

Young‐onset colorectal cancer is associated with a personal history of type 2 diabetes

Leptin and adiponectin dynamics at patients with rectal neoplasm - Gender differences

Effects of family history of diabetes on pancreatic β-cell function and diabetic ketoacidosis in newly diagnosed patients with type 2 diabetes: a cross-sectional study in China

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