Risk Of Pancreatic Cancer Research Articles

The effect of hormonal contraception on the risk of breast cancer: A review

Hormonal-induced changes in the breast occur due to both endogenous and exogenous sex hormones. For two decades, the safety of hormonal contraceptives (HC) in terms of their effect on breast tissue has been discussed in the literature. The pleiotropic effect of the components in the combined HC, on the one hand, prevents unwanted pregnancy; on the other hand, they help to maintain good health of women of childbearing age due to a wide range of non-contraceptive effects (eliminating hyperandrogenism manifestations, reducing the pain severity during menstruation and the menstrual blood loss, the risk of recurrence of functional ovarian cysts, oncoprotective effect due to reducing the risk of ovarian, endometrial, colorectal, pancreatic, and lung cancer). However, according to epidemiological studies, in addition to the beneficial effects, there are risks that require further study, including the controversial impact of HC on the oncogenesis and progression of breast cancer. In addition, some young women with breast cancer experience induced menopause after antitumor treatment. However, amenorrhea is not a marker for complete disabling of ovarian function, and pregnancy is associated with a risk of disease recurrence or progression. Therefore, in each case, it is necessary to determine the need for an effective and safe method of contraception.

Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival.

Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated. Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR). Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002). High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival. Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.

The impact of diabetes status on total and site-specific cancer risk in the elderly population: A nationwide cohort study

AimsWe aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with risk of total and site-specific cancer in the Korean population aged 65 years and above. MethodsThis study included 1,232,173 subjects aged ≥ 65 years who underwent a general health screening program. Diabetes status was categorized as normal glucose tolerance, impaired fasting glucose, new-onset diabetes, diabetes duration of < 5 years, and diabetes duration of ≥ 5 years. Cox proportional hazards models were used to investigate the association of diabetes status with cancer risk. ResultsThe risk of total cancer increased as diabetes status worsened, as did the risks of liver, biliary, and pancreatic cancer. Risks of liver, biliary, and pancreatic cancer were significantly higher in subjects aged 65–74 years than in those aged ≥ 75 years. The relationship of diabetes status with overall cancer incidence was found to significantly interact with sex. Among subjects with diabetes, the risks of liver and lung cancer were significantly higher in men than in women regardless of diabetes duration. ConclusionsDiabetes status is associated with increased risk of cancer in the elderly. There are age and sex differences in the risk of total and site-specific cancers, including liver, biliary, and pancreatic cancer. This study highlights the importance of cancer screening for elderly subjects with diabetes.

Association between multiple sclerosis and cancer risk: An extensive review/meta and Mendelian randomization analyses.

Observational investigations examining cancer risk among multiple sclerosis (MS) patients have produced contradictory findings. Herein, we performed an extensive review and meta-analysis to evaluate the correlation and causation between MS and cancer incidence. We systematically screened for published articles examining cancer incidences among MS patients within the Cochrane Library, PubMed, and Embase databases. Next, we employed STATA v.16.0 for data analysis. Following meta-analysis, we performed a two-sample Mendelian randomization (MR) analysis to uncover the underlying mechanism behind the MS-mediated regulation of certain cancers. Overall, we selected 18 articles encompassing 14 individual cancers incidences and a total of 368,952 patients for meta-analysis. Based on our analysis, there was reduced pancreatic (ES=0.68; 95% CI: 0.49-0.93; I 2=0%) and ovarian cancer (ES=0.65; 95% CI: 0.53-0.80; I 2=86.7%) co-occurrences among MS patients. Meanwhile, the incidences of breast (ES=1.10; 95% CI: 1.01-1.21; I 2=60.9%) and brain cancers (ES=1.94; 95% CI: 1.12-3.37; I 2=56.1%) were elevated among the same population. However, MR analysis revealed the opposite relation between MS and breast cancer risk (OR=0.94392; 95% CI: 0.91011-0.97900, P=0.002). Moreover, it revealed strong incidence of lung cancer (OR=1.0004; 95% CI: 1.0001-1.0083, P=0.001) among MS patients, as evidenced by the inverse variance weighting estimator. Lastly, MR found that other forms of cancers were not significantly related to MS. Using meta-analysis, we demonstrated that MS patients exhibited enhanced pancreatic and ovarian cancer risk, and diminished breast and brain cancer risk. However, using MR analysis, we discovered an inverse relation between MS and breast cancer risk, and additionally saw an uptick in lung cancer co-occurrence among MS patients.

Surgical Risks and Survival Outcomes in Robotic Pancreaticoduodenectomy for the Aged Over 80: A Retrospective Cohort Study.

Whether to execute pancreaticoduodenectomy or not for older people could pose a dilemma. This study clarifies the safety and justification of robotic pancreaticoduodenectomy (RPD) for older individuals over 80. A total of 500 patients undergoing RPD were divided into group O (≥ 80 y/o) and group Y (< 80 y/o) for comparison. There were 62 (12.4%) patients in group O. Surgical mortality was 1.6% for overall patients and higher in group O, 6.5% vs 0.9%; p = 0.001. The surgical complication was comparable between groups O and Y. Delayed gastric emptying and bile leakage were higher in group O, 9.7% vs 2.5%; p = 0.004, and 6.5% vs 0.9%; p = 0.001, respectively. Length of stay was also longer in group O, with a median of 26 vs 19 days; p = 0.001. Survival outcome after RPD was poorer in group O for overall periampullary adenocarcinomas, with a 5-year survival of 48.1% vs 51.2%; p = 0.025 and also for the subgroup of pancreatic head adenocarcinoma, with a 3-year survival of 27.4% vs 42.5%; p = 0.030. RPD is safe and justified for the selected octogenarians and even nonagenarians, whoever is fit for a major operation. Nevertheless, pancreatic head cancer and higher mortality risk for the aged over 80 with advanced ASA score ≥ 3 should be informed as part of counselling in offering RPD.

Major dietary patterns in the United Kingdom Women's Cohort Study showed no evidence of prospective association with pancreatic cancer risk

Diet is a modifiable risk factor for pancreatic cancer. We hypothesized that specific dietary patterns would increase/decrease pancreatic cancer risk. We evaluated the association of dietary patterns with pancreatic cancer risk in the UK Women's Cohort Study. Dietary patterns were assessed at enrollment using: (1) self-reported practice of vegan/vegetarian dietary habits, (2) diet quality indices (World Health Organization Healthy Diet Indicator and Mediterranean Diet Score), and (3) principal component analysis-derived dietary patterns. The association of dietary patterns with pancreatic cancer incidence was quantified using Cox regression survival analysis. Over a median follow-up of 19 years of 35,365 respondents, there were 136 incident cases of pancreatic cancer. No association between dietary habits/quality and pancreatic cancer incidence was evident after adjustments (hazard ratio (95% confidence interval): self-reported omnivores vs vegan/vegetarian dietary habit: 1.13 (0.73-1.76); per-unit increase in World Health Organization Healthy Diet Indicator scores: 0.99 (0.91-1.09); per-unit increase in Mediterranean Diet Score: 0.92 (0.83-1.02). Similarly, no association of principal component analysis-derived dietary patterns with pancreatic cancer risk was evident ("prudent:" 1.02 [0.94-1.10]; ``meat-based:'' 1.00 [0.92-1.09]; ``fast-food, sugar-sweetened beverages, and carbohydrate-rich snacks:'' 0.96 [0.86-1.07]; ``cereal and dairy-rich:'' 1.04 [0.94-1.16], and ``low-diversity and lowfat:'' 1.00 [0.89-1.13]). In this prospective cohort of women, several major dietary patterns were of poor quality. There was no evidence of a prospective association between any of the dietary patterns explored and pancreatic cancer incidence.

Epidemiology of pancreatic cancer

At present, pancreatic cancer morbidity continues to grow at an accelerated rate worldwide. At the same time the five-year survival rate of patients with pancreatic cancer remains low, occupying a significant position in the mortality structure. This is mainly due to late diagnosis, as well as to the increasing proportion of the elderly population. Factors influencing the prognosis include age, sex, blood group, family history and genetic predisposition, diabetes, smoking, alcohol, chronic pancreatitis, and obesity. Objective: to present up-to-date data on pancreatic cancer epidemiology in the world, Russian Federation and Omsk region. Materials and methods: the article analyzes the data of morbidity, mortality and five-year survival rate of patients with pancreatic cancer for the years 2020-2021. Results: the growth of morbidity and persistent low survival rates emphasize the necessity of determining methods of screening patients with high risk of pancreatic cancer, developing methods of early detection and improving both surgical and drug treatment of these patients, as well as prophylaxis.

Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years

Diabetes medications may modify the risk of certain cancers. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 for studies evaluating associations between diabetes medications and the risk of breast, lung, colorectal, prostate, liver, and pancreatic cancers. A total of 92 studies (3 randomized controlled trials, 64 cohort studies, and 25 case–control studies) were identified in the systematic review, involving 171 million participants. Inverse relationships with colorectal (n = 18; RR = 0.85; 95% CI = 0.78–0.92) and liver cancers (n = 10; RR = 0.55; 95% CI = 0.46–0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (n = 6; RR = 0.87; 95% CI = 0.80–0.95), lung (n = 6; RR = 0.77; 95% CI = 0.61–0.96) and liver (n = 8; RR = 0.83; 95% CI = 0.72–0.95) cancers. Insulins were negatively associated with breast (n = 15; RR = 0.90; 95% CI = 0.82–0.98) and prostate cancer risks (n = 7; RR = 0.74; 95% CI = 0.56–0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (n = 5; RR = 1.26; 95% CI = 1.01–1.57), and between insulins and liver (n = 7; RR = 1.74; 95% CI = 1.08–2.80) and pancreatic cancers (n = 8; RR = 2.41; 95% CI = 1.08–5.36). Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk.

Overview of Pancreatic Cancer Epidemiology in Europe and Recommendations for Screening in High-Risk Populations.

Pancreatic cancer is the seventh most common cause of death in the group of oncological diseases. Due to the asymptomatic course, early diagnosis is difficult. Currently, early detection methods are only used in high-risk groups. A literature review based on the available results of observational studies on patients with pancreatic cancer and people from high-risk groups was used to summarize the knowledge on risk factors. The GLOBOCAN 2020 data were used to assess the epidemiological situation in Europe. A summary of screening recommendations was prepared based on the available documents from medical organizations and associations. Pancreatic cancer risk factors are divided into two main groups: non-modifiable factors, e.g., hereditary factors and age, which increase the risk of developing this disease, and modifiable factors-BMI, smoking, and alcohol consumption. Hereditary factors account for 10% of pancreatic cancer cases. The highly specialized methods of early detection, (MRI, CT, or EUS) are used for screening high-risk populations. Of all the imaging methods, EUS is considered the most sensitive for pancreatic cancer and allows an accurate assessment of the size of even small lesions (<30 mm) and the extent of tumour infiltration into blood vessels. The available studies vary on the level of sensitivity and specificity of these methods for the diagnosis of pancreatic cancer. EUS, MRI, and CT are also expensive procedures and in some patients can be invasive, which is one of the arguments against the introduction of population screening programs based on imaging methods. Therefore, it is important to look for viable solutions that would improve early detection. This is important from the point of view of healthcare systems in Europe, where almost 29% of all global pancreatic cancer cases are reported.

Genetic ablation of ketohexokinase C isoform impairs pancreatic cancer development

Although dietary fructose is associated with an elevated risk for pancreatic cancer, the underlying mechanisms remain elusive. Here, we report that ketohexokinase (KHK), the rate-limiting enzyme of fructose metabolism, is a driver of PDAC development. We demonstrate that fructose triggers KHK and induces fructolytic gene expression in mouse and human PDAC. Genetic inactivation of KhkC enhances the survival of KPC-driven PDAC even in the absence of high fructose diet. Furthermore, it decreases the viability, migratory capability, and growth of KPC cells in a cell autonomous manner. Mechanistically, we demonstrate that genetic ablation of KHKC strongly impairs the activation of KRAS-MAPK pathway and of rpS6, a downstream target of mTORC signaling. Moreover, overexpression of KHKC in KPC cells enhances the downstream KRAS pathway and cell viability. Our data provide new insights into the role of KHK in PDAC progression and imply that inhibiting KHK could have profound implications for pancreatic cancer therapy.

Risk of pancreatic cancer in people with new-onset diabetes: A Danish nationwide population-based cohort study

BackgroundNew onset diabetes (NOD) in people 50 years or older may indicate underlying pancreatic ductal adenocarcinoma (PDAC). The cumulative incidence of PDAC among people with NOD remains uncertain on a population-based level. MethodsThis was a nationwide population-based retrospective cohort study based on the Danish national health registries. We investigated the 3-year cumulative incidence of PDAC in people 50 years or older with NOD. We further characterised people with pancreatic cancer-related diabetes (PCRD) in relation to demographic and clinical characteristics, including trajectories of routine biochemical parameters, using people with type 2 diabetes (T2D) as a comparator group. ResultsDuring a 21-year observation period, we identified 353,970 people with NOD. Among them, 2105 people were subsequently diagnosed with pancreatic cancer within 3 years (0.59%, 95% CI [0.57–0.62%]). People with PCRD were older than people with T2D at diabetes diagnosis (median age 70.9 vs. 66.0 years (P < 0.001) and had a higher burden of comorbidities (P = 0.007) and more prescriptions of medications used to treat cardiovascular diseases (all P < 0.001). Distinct trajectories of HbA1c and plasma triglycerides were observed in PCRD vs. T2D, with group differences observed for up to three years prior to NOD diagnosis for HbA1c and up to two years for plasma triglyceride levels. ConclusionsThe 3-year cumulative incidence of PDAC is approximately 0.6% among people 50 years or older with NOD in a nationwide population-based setting. Compared to T2D, people with PCRD are characterised by distinct demographic and clinical profiles, including distinctive trajectories of plasma HbA1c and triglyceride levels.

Association of a genetic variant in the adenosine triphosphate transmembrane glycoprotein and risk of pancreatic cancer

Association of a genetic variant in the adenosine triphosphate transmembrane glycoprotein and risk of pancreatic cancer

CPC12 Coinheritance of BRCA2 and CYLD germline pathogenic variants associated with targetable metastatic malignant cylindroma

Abstract CYLD cutaneous syndrome (CCS) presents during puberty with the development of hair follicle tumours, including cylindromas, spiradenomas or trichoepitheliomas, and is associated with pathogenic variants in the tumour suppressor gene CYLD. Germline pathogenic variants of BRCA2 are associated with an increased risk of breast, ovarian, pancreatic and prostate cancer. Coinheritance of pathogenic variants in both genes has not been previously reported, and here, we present a 29-year-old man with metastatic malignant cylindroma, where knowledge of the germline variants has targetable therapeutic implications. The proband presented with cylindromas on his scalp from the age of 8 years, inherited from his mother who had CCS. The proband’s father and paternal grandmother both had early-onset breast cancer. The proband’s 33-year-old sister had been diagnosed with breast cancer and CCS; genetic testing revealed germline pathogenic variants in both BRCA2 and CYLD. Aged 28 years, the proband presented with a growing, ulcerated cylindroma on the scalp. Histology revealed a biphasic neoplasm, showing malignant cylindroma with high-grade features arising within a pre-existing benign cylindroma. The malignant epithelioid component of the tumour showed brisk mitotic activity (25 mitoses per mm2) and large infiltrative nests with central comedo-type necrosis. Immunohistochemistry showed positivity for epithelial membrane antigen, CK7, p63 and patches of CK5/6, whereas carcinoembryonic antigen, S100 and human melanoma black-45 were negative. Several weeks after excision of the malignant scalp cylindroma, a lump presented on the left side of the patient’s neck; biopsy revealed histology consistent with the malignant scalp cylindroma. Radiological imaging revealed metastatic deposits of malignant cylindroma in the right axilla, both lungs and the brain. Genetic testing of the proband revealed germline pathogenic variants in both BRCA2 and CYLD, as seen in his sister. The patient received radiotherapy for the tumour in his neck, with partial resolution of symptoms and gamma-knife ablation of brain metastases. DNA extracted from the patient’s tumour was analysed using a high-resolution single-nucleotide polymorphism array, which demonstrated loss of heterozygosity including the BRCA2 and CYLD loci. The germline and somatic pathogenic variants in this patient support the use of unlicensed therapeutics that target BRCA deficiency, such as poly-ADP ribose polymerase inhibitors, which have not previously been used to treat malignant cylindroma. This case emphasizes the importance of recognizing coinheritance of tumour suppressor genes in rare genetic conditions, as this can provide novel management options and improve patient outcomes.

Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.

There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.

Relationship between ABO Blood Group Alleles and Pancreatic Cancer Is Modulated by Secretor (FUT2) Genotype, but Not Lewis Antigen (FUT3) Genotype.

In Western populations, pancreatic ductal adenocarcinoma (PDAC) risk has been found to be greater among individuals with non-O blood types than those with O blood type. However, the association has not been fully evaluated with respect to FUT2 (determining secretor status) and FUT3 (determining Lewis antigens) status, two biologically important genes in the expression of ABO blood groups with PDAC. We examined interactions in data from 8,027 cases and 11,362 controls in large pancreatic cancer consortia (PanScan I-III and PanC4) by using genetic variants to predict ABO blood groups (rs505922 and rs8176746), secretor status (rs601338), and Lewis antigens (rs812936, rs28362459, and rs3894326). Multivariable logistic regression was used to estimate ORs and 95% confidence intervals (CI) of the risk of PDAC adjusted for age and sex. We examined multiplicative interactions of ABO with secretor status and Lewis antigens by considering each product term between ABO and secretor and between ABO and Lewis antigens individually. We found that the increased risk associated with non-O blood groups was somewhat stronger among secretors than nonsecretors [ORs, 1.28 (95% CI, 1.15-1.42) and 1.17 (95% CI, 1.03-1.32) respectively; Pinteraction = 0.002]. We did not find any interactions between ABO and Lewis antigens. Our large consortia data provide evidence of effect modification in the association between non-O blood type and pancreatic cancer risk by secretor status. Our results indicate that the association between ABO blood type and PDAC risk may vary by secretor status, but not by Lewis antigens.

External validation of genetically predicted protein biomarkers for pancreatic cancer risk using aptamer-based plasma levels: A prospective analysis in the Atherosclerosis Risk in Communities Study.

Genetically predicted proteins have been associated with pancreatic cancer risk previously. We aimed to externally validate the associations of 53 candidate proteins with pancreatic cancer risk using directly measured, prediagnostic levels. We conducted a prospective cohort study of 10 355 US Black and White men and women in the Atherosclerosis Risk in Communities (ARIC) study. Aptamer-based plasma proteomic profiling was previously performed using blood collected in 1993 to 1995, from which the proteins were selected. By 2015 (median: 20 years), 93 incident pancreatic cancer cases were ascertained. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for protein tertiles, and adjust for age, race, and known risk factors. Of the 53 proteins, three were statistically significantly, positively associated with risk-GLCE (tertile 3 vs 1: HR = 1.88, 95% CI: 1.12-3.13; P-trend = 0.01), GOLM1 (aptamer 1: HR = 1.98, 95% CI: 1.16-3.37; P-trend = 0.01; aptamer 2: HR = 1.86, 95% CI: 1.07-3.24; P-trend = 0.05), and QSOX2 (HR = 1.96, 95% CI: 1.09-3.58; P-trend = 0.05); two were inversely associated-F177A (HR = 0.59, 95% CI: 0.35-1.00; P-trend = 0.05) and LIFsR (HR = 0.55, 95% CI: 0.32-0.93; P-trend = 0.03); and one showed a statistically significant lower risk in the middle tertile-endoglin (HR = 0.50, 95% CI: 0.29-0.86); by chance, we expected significant associations for 2.65 proteins. FAM3D, IP10, sTie-1 (positive); SEM6A and JAG1 (inverse) were suggestively associated with risk. Of these 11, 10 proteins-endoglin, FAM3D, F177A, GLCE, GOLM1, JAG1, LIFsR, QSOX2, SEM6A and sTie-1-were consistent in direction of association with the discovery studies. This prospective study validated or supports 10 proteins as associated with pancreatic cancer risk.

AI predicts pancreatic cancer risk.

AI predicts pancreatic cancer risk.

The Association Between Oral Anaerobic Bacteria and Pancreatic Cancer

Reports have shown increased positive correlations with the salivary microbiota and pancreatic carcinogenesis. A European study showed that high levels of Porphyromonas gingivalis were correlated with periodontium damage and were associated with a risk of pancreatic cancer (two-fold). A recent study, using oral mouthwash samples (n = 361 with pancreatic adenocarcinoma), determined that the presence of P. gingivalis and Aggregatibacter actinomycetemcomitans along with Fusobacteria and Leptotrichia were a risk factor for pancreatic cancer. The link between pancreatic cancer and periodontitis has been documented. Interestingly, periodontitis presents with inflammation and microbial dysbiosis, both of which have been characterized in pancreatic cancer. This review highlights multiple roles in which oral anaerobic bacteria can spread to the pancreas and contribute to pancreatic cancer.

Cancer risk and characteristics in older female BRCA1/2 mutation carriers.

10610 Background: Cancer risk and characteristics in older females with BRCA1/2 mutations are less well studied, and the role of risk-reducing strategies in this population remains unclear. Methods: From a database of 1070 female carriers of BRCA1/2 pathogenic (PV) or likely pathogenic variants (LPV) seen at Nancy and James Grosfeld Cancer Genetics Center in Beaumont Health from January 2006 to December 2021, we identified 283 females who lived to age 65 or older. We analyzed cancer risk and clinical characteristics, focusing on females with cancer diagnosed at age 65 or older. Results: Of the 283 BRCA1/2 carriers, 229 (81%) had a cancer diagnosis, out of which 84 (37%) were diagnosed at age 65 or older. Of all the breast cancer diagnoses (n = 173), 45 (26%) were diagnosed at age 65 or older. Among these 45 patients, median age at diagnosis was 69 years (65-87); majority were BRCA2 carriers (62%), with invasive ductal carcinoma (80%), ER-positive (58%), PR-negative (55%), HER2-negative (97%), high grade (55%) and had stage I or II disease (78%). Fifteen patients (38%) were triple-negative. A minority (32%) received adjuvant chemotherapy, 43% received adjuvant endocrine therapy, and 54% received adjuvant radiation. During a median follow-up of 205 months for all breast cancers (n = 173), there were 52 recurrences, 28 of these (54%) were diagnosed at age 65 or older, of which 13 were contralateral (median time to recurrence: 140 months); 5 were local/regional (median time: 186 months) and 10 were metastatic (median time: 76 months). Ten of the 13 contralateral recurrences (77%) were in BRCA1 carriers. Of the ovarian cancer diagnoses (n = 69), 27 (39%) were diagnosed at age 65 or older. Among these 27 patients, median age at diagnosis was 71 years (65-87); majority were BRCA2 carriers (74%), had serous carcinoma (84%), with stage III or IV disease (96%). Of all ovarian cancers (n = 69), there were 15 recurrences (22%), 9 of them (60%) were diagnosed at age 65 or older. Of the 8 pancreatic cancers, 6 were diagnosed at age 65 or older. Of the 283 BRCA1/2 carriers, 249 still had at least one breast at the time of genetic testing, and 34% elected for risk-reducing mastectomy (RRM). Of the 177 patients with intact ovaries, 71% opted for risk-reducing salpingo-oophorectomy (RRSO). Compared to BRCA carriers with cancer diagnosed under age 65, a smaller proportion of those diagnosed at age 65 or older opted to undergo RRM (26% vs. 40%) or RRSO (67% vs. 78%). Conclusions: Our study reveals that female BRCA1/2 mutation carriers over age 65 continue to retain a significant risk of cancer, including breast, contralateral breast, ovarian, and pancreatic cancer. This finding supports the importance of continued high-risk surveillance and risk-reducing interventions in this growing demographic. Further studies are needed to better define the cancer risks and optimal management of older females with BRCA1/2 mutations.

Predicting the risk of pancreatic cancer in patients with new-onset diabetes based on CT image.

e16320 Background: While long-standing diabetes mellitus (LsDM) is an etiologic factor for PC, new-onset diabetes (NoDM) has been considered as a manifestation and harbinger of this cancer as well. Current evidence support that the PC-associated NoDM was mainly caused by disease of the exocrine pancreas, which was different from the typical type 2 DM. Therefore, we hypothesize that, in the NoDM patients, CT image features of “normal” pancreas from PC-associated NoDM patients might be different from that of the new-onset type 2 DM. We sought to develop and validate a risk prediction model to facilitate the distinction between NoDM vs potential early PC-associated NoDM on pancreatic CT imaging. Methods: We retrospectively collected CT imaging from three types of patients at Guangdong Provincial People's Hospital between January 2015 and December 2022: PC patients with pathological diagnosis of pancreatic ductal adenocarcinoma (n=249: 139 patients without DM, 63 patients with NoDM, 47 patients with LsDM), NoDM patients diagnosed with PC within 3 years (n=12), NoDM patients without development of cancer within the next 5 years (n=151). We used four different machine learning algorithms, including support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and generalized linear model (GLM), and gradient boost methods, to build prediction models based on PC pateints and cancer-free NoDM patients. The algorithm with best ROC was used to build a final model, which was validated in the “normal” CT images of NoDM patients prior to their diagnosis of PC within 3 years. Results: In PC cases, the radiomics features exclusive to NoDM-PC cases were selected using a non-parametric test, and 134 radiomics features were retained (86 from arterial and 48 from venous phases, respectively). The RF algorithm showed best prediction skill (AUC of ROC: 0.952). Based on the variable importance measures in the RF algorithm, a risk-scoring model was generated for NoDM patients as a tool to differentiate between PC patients and cancer-free DM patients. As a result of validation, the scores calculated based on the “normal” CT images of NoDM patients prior to their diagnosis of PC within 3 years, were significantly higher than the scores from CT images of NoDM patients who were cancer-free within the next 5 years (P &lt; 0.01). Conclusions: In NoDM patients, even the PC lesion was nonvisible on CT, the radiomics features of “normal” pancreas of PC patients were different from that of the real DM patients. Our model has the potential for identifying individuals with PC in the whole NoDM population.