Reduction In Pancreatic Cancer Risk Research Articles

The causal relationship between cathepsins and digestive system tumors: a Mendelian randomization study.

Multiple studies have confirmed the significant role of cathepsins in the development and progression of digestive system tumors. However, further investigation is needed to determine the causal relationships. We conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from a genome-wide association study (GWAS) to assess the causal associations between nine cathepsins (cathepsin B, E, F, G, H, L2, O, S, and Z) and six types of digestive system tumors, including hepatocellular carcinoma (HCC), pancreatic cancer (PCa), biliary tract cancer (BTC), colorectal cancer (CRC), gastric carcinoma (GC), and esophageal cancer (EC). We employed the following methods including inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran's Q, MR-PRESSO, MR-Egger intercept test and leave-one-out sensitivity analysis. The STROBE-MR checklist for the reporting of MR studies was used in this study. The risk of HCC increased with high levels of cathepsin G (IVW: p = 0.029, odds ratio (OR) = 1.369, 95% confidence interval (CI) = 1.033-1.814). Similarly, BTC was associated with elevated cathepsin B levels (IVW: p = 0.025, OR = 1.693, 95% CI = 1.070-2.681). Conversely, a reduction in PCa risk was associated with increased cathepsin H levels (IVW: p = 0.027, OR = 0.896, 95% CI = 0.812-0.988). Lastly, high levels of cathepsin L2 were found to lower the risk of CRC (IVW: p = 0.034, OR = 0.814, 95% CI = 0.674-0.985). Our findings confirm the causal relationship between cathepsins and digestive system tumors, which can offer valuable insights for the diagnosis and treatment of digestive system tumors.

O089 Relationship of metformin with the risk of pancreatic cancer in patients with diabetes and/or chronic pancreatitis: a systematic review

Abstract Introduction Metformin is the first-line treatment in patients with Type 2 diabetes. However, controversy exists regarding its role in reducing the risk of pancreatic cancer or improving pancreatic cancer survival in patients with Type 2 diabetes or chronic pancreatitis. This systematic review aimed to define the risk of pancreatic cancer and survival from pancreatic cancer in patients with diabetes or chronic pancreatitis receiving metformin. Methods Systematic searches of Medline and Cochrane Library databases were undertaken to identify studies reporting on the use of metformin and its impact on pancreatic cancer risk and/or survival in patients with diabetes or chronic pancreatitis. Results Thirty studies, reporting on a total of 5,969,712 patients (1,362,308 with diabetes or chronic pancreatitis, and 4,597,095 controls), were included. Eleven studies assessed the risk of developing pancreatic cancer. Of these, six found a significant reduction in the risk of developing pancreatic cancer in those taking metformin, whereas five studies found no such reduction in pancreatic cancer risk. Another 19 studies evaluated the impact of metformin on pancreatic cancer survival. Twelve of these found evidence of benefit in those receiving metformin, whereas seven found no survival benefit. Formal pooling could not be undertaken due to high statistical and clinical heterogeneity. Conclusion The relationship between the use of metformin and the incidence of pancreatic cancer is complex and multifactorial. However, the currently available evidence is not sufficient for definitive conclusions on this relationship. Take-home message Current evidence is not robust enough to recommend the use metformin as prophylaxis for pancreatic cancer or to improve survival in patients with pancreatic cancer.

Abstract 5870: Diet quality and pancreatic cancer incidence in the Multiethnic Cohort

Abstract Background: Pancreatic cancer is one of the deadliest cancers, and its incidence has been increasing steadily in the past decade. While some dietary components have been implicated as risk factors for pancreatic cancer, epidemiological data on the role of overall diet quality in pancreatic cancer etiology are limited, especially from population-based prospective studies. This study examined the relationship between diet quality and pancreatic cancer incidence in the Multiethnic Cohort Study (MEC). Methods: Data were analyzed from 177,313 African American, Native Hawaiian, Japanese American, Latino, and White men and women aged 45-75 years who completed a quantitative food frequency questionnaire at cohort entry. Diet quality was assessed by a priori diet quality indices (DQIs), the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED) score, the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII®). These five DQIs were investigated because of their potential to capture differences in various nutritional patterns across different racial/ethnic groups. Multivariate Cox models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the DQIs and pancreatic cancer incidence adjusted for age, sex, race/ethnicity, education, diabetes status, family history of pancreatic cancer, vigorous physical activity, smoking status with pack years, total energy intake, body mass index (BMI), and alcohol consumption. Stratified analyses were done by sex, race/ethnicity, smoking status and BMI. Results: During an average follow up of 19.3 years, 1,782 incident pancreatic cancer cases were identified. Overall, we did not observe statistically significant associations between the DQIs and pancreatic cancer risk. In subgroup analyses comparing the highest vs. lowest quintiles of the scores, a protective association was observed with the DASH for ever smokers (HR = 0.75, 95% CI: 0.60-0.92) and individuals with BMI ≥ 25 kg/m2 (HR = 0.77, 95% CI: 0.63-0.94), but not for never smokers (HR = 1.04, 95% CI: 0.82-1.31, P for heterogeneity = 0.004) or those with BMI < 25 kg/m2 (HR = 1.21, 95% CI: 0.94-1.56, P for heterogeneity = 0.097). There were no differences in associations by sex or race/ethnicity (P for heterogeneity ≥ 0.43). Conclusion: In this large prospective study, we did not find reduction in pancreatic cancer risk associated with healthier diet as assessed by the 5 DQIs. There is some indication that adherence to the DASH diet may potentially be protective against pancreatic cancer among ever smokers or individuals classified as overweight or obese. Further investigations are needed to confirm these findings. Citation Format: Heather Steel, Song-Yi Park, Tiffany Lim, Daniel Stram, Loic Le Marchand, Anna H. Wu, V. Wendy Setiawan. Diet quality and pancreatic cancer incidence in the Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5870.

Composite Score of Healthy Lifestyle Factors and the Risk of Pancreatic Cancer in a Prospective Cohort Study

Abstract While the associations between individual lifestyle factors and risk of pancreatic cancer were studied extensively, their combined impact has not been examined. We evaluated the association of a composite score of healthy lifestyle factors, including body mass index, cigarette smoking, the Alternative Healthy Eating Index-2010 (AHEI-2010), sleep duration, and physical activity with pancreatic cancer risk in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63,257 Chinese aged 45 to 74 years at enrollment in 1993 to 1998 with up to 25 years of follow up. Cox proportional hazard regression method was used to estimate HR and its 95% confidence interval (CI) with adjustment for multiple potential confounders. We identified 316 incident pancreatic cancer cases among the cohort participants after a mean 17 years of follow up. Individuals with higher composite scores representing healthier lifestyle were at significantly lower risk of pancreatic cancer. The multivariate-adjusted HRs (95% CIs) of pancreatic cancer incidence for the composite scores 2, 3, 4, 5, 6 to 7 were 0.60 (0.50–0.91), 0.48 (0.32–0.71), 0.45 (0.31–0.67), 0.41 (0.27–0.62), and 0.38 (0.24–0.62), respectively, compared with the scores 0 to 1 (Ptrend < 0.0001). The inverse association was more apparent among participants without diabetes history and was robust in men and women as well as in alcohol drinkers and nondrinkers. In summary, the association for pancreatic cancer risk was stronger for the aggregated than individual healthy lifestyle factors. These findings suggest that a more comprehensive lifestyle modification strategy would be more effective for prevention of pancreatic cancer than the change of a single lifestyle factor. Prevention Relevance: In this large prospective Asian study, we calculated a composite score of healthy lifestyle factors, including body mass index, cigarette smoking, the Alternative Healthy Eating Index-2010 (AHEI-2010), sleep duration, and physical activity and found this composite score was associated with a significant reduction in pancreatic cancer risk, by as much as 62%. This finding suggests that public health programs emphasizing comprehensive lifestyle modification strategy would be more effective for prevention of pancreatic cancer than the change of a single lifestyle factor.

Physical activity and risk of pancreatic cancer: a systematic review and meta-analysis.

Physical activity may prevent pancreatic cancer by regulating body weight and decreasing insulin resistance, DNA damage, and chronic inflammation. Previous meta-analyses found inconsistent evidence for a protective effect of physical activity on pancreatic cancer but those studies did not investigate whether the association between physical activity and pancreatic cancer varies by smoking status, body mass index (BMI), or level of consistency of physical activity over time. To address these issues, we conducted an updated meta-analysis following the PRISMA guidelines among 30 distinct studies with a total of 10,501 pancreatic cancer cases. Random effects meta-analysis of cohort studies revealed a weak, statistically significant reduction in pancreatic cancer risk for high versus low levels of physical activity (relative risk (RR) 0.93, 95 % confidence interval (CI) 0.88-0.98). By comparison, case-control studies yielded a stronger, statistically significant risk reduction (RR 0.78, 95 % CI 0.66-0.94; p-difference by study design = 0.07). When focusing on cohort studies, physical activity summary risk estimates appeared to be more pronounced for consistent physical activity over time (RR 0.86, 95 % CI 0.76-0.97) than for recent past physical activity (RR 0.95, 95 % CI 0.90-1.01) or distant past physical activity (RR 0.95, 95 % CI 0.79-1.15, p-difference by timing in life of physical activity = 0.36). Physical activity summary risk estimates did not differ by smoking status or BMI. In conclusion, physical activity is not strongly associated with pancreatic cancer risk, and the relation is not modified by smoking status or BMI level. While overall findings were weak, we did find some suggestion of potential pancreatic cancer risk reduction with consistent physical activity over time.

Association of Genetic Polymorphisms in UDP-Glucuronosyltransferases 2B17 with the Risk of Pancreatic Cancer in Chinese Han Population.

This study is aimed to investigate the association between polymorphisms in UGT2B17 and the risk of developing pancreatic cancer in Chinese Han population. A hospital-based case-control study was conducted, and 1579 healthy controls and 406 pancreatic cancer patients were enrolled. Real-time PCR was applied to identify the genetic polymorphisms in the subjects, and multivariable logistic regression analysis was performed to investigate the association between UGT2B17 polymorphisms and susceptibility to pancreatic cancer. The prevalence of the UGT2B17 del/del, del/ins, and ins/ins in cases were 72.9%, 24.0%, and 3.1%, respectively, and in controls 66.6%, 30.7%, and 2.7%, respectively. Multivariable logistic regression revealed that, compared with the del/del genotype, the del/ins genotype in UGT2B17 is related to a significant reduction in pancreatic cancer risk (OR = 0.77, 95% CI = 0.60 - 0.99; P = 0.04). In the female subjects, compared with the del/del genotype, the del/ins genotype was related to a substantial reduction in pancreatic cancer risk (OR = 0.59, 95% CI = 0.39 - 0.90, P = 0.01). All these results indicate a higher ratio of UGT2B17 deletion polymorphisms in Asians. UGT2B17 deletion polymorphisms are associated with the risk of developing pancreatic cancer in Chinese Han population, especially in the female population.

Highlights of This Issue

Studies suggest that allergies are associated with reduced pancreatic cancer risk. To explore this relationship, Cotterchio and colleagues conducted a case–control study where pancreatic cancer cases identified through the Ontario Cancer Registry were evaluated using questionnaires focused on lifetime allergy history, allergy medications, and pancreatic cancer history. The authors found that hay fever was associated with a significant reduction in pancreatic cancer risk. Also, dust/mold allergy and animal allergies were associated with reduced pancreatic cancer risks. These findings support that certain allergies are associated with reduced pancreatic cancer risk.Men with Lynch syndrome, who carry DNA mismatch repair (MMR) gene mutations, may be at heightened risk of prostate cancer. To explore this, Ryan and colleagues performed a meta-analysis and examined MMR-deficiency status and prostate cancer in men with MMR gene mutations. The authors report that 73% of prostate cancer tumors in mutation carriers were MMR-deficient, which equates to carriers having a 3.67-fold increased risk of prostate cancer. The authors estimated a 2.28-fold increased risk of prostate cancer for all men from mutation-carrying families. This report supports consideration of prostate cancer as part of Lynch syndrome.Lifestyle factors that affect prognosis after treatment for ductal carcinoma in situ (DCIS) breast cancer were examined by Hart McLaughlin and colleagues. The authors report on the association between body mass index (BMI), physical activity, and alcohol intake and risk of a second breast cancer diagnosis among DCIS survivors in the Wisconsin In Situ Cohort. Over a 6.7-year follow-up period, a significant trend of increasing risk of a second diagnosis was found with post-diagnosis alcohol intake. Among premenopausal women, increased pre-diagnosis BMI was associated with a reduced risk of a second diagnosis.Imbalances in tryptophan metabolism have been linked to several cancers. Chuang and colleagues conducted a nested case–control study within the EPIC cohort and measured circulating levels of tryptophan and tryptophan metabolites and their association with lung cancer. The study found that both tryptophan and the kynurenine/tryptophan ratio were associated with lung cancer risk. This work supports that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk.

Association between Allergies and Risk of Pancreatic Cancer

Less than 10% of pancreatic cancer cases survive 5 years, yet its etiology is not well understood. Studies suggest allergies are associated with reduced pancreatic cancer risk. Our study collected additional information on allergies (including skin prick test results and differentiation of allergic/nonallergic asthma), and is the first to assess possible confounding by allergy medications. A population-based case-control study was designed to comprehensively assess the association between allergy and pancreatic cancer risk. Pancreas cancer cases were diagnosed during 2011 to 2012, and identified through the Ontario Cancer Registry (345 cases). Population-based controls were identified using random digit dialing and age/sex frequency matched to cases (1,285 controls). Questionnaires collected lifetime allergy history (type of allergy, age at onset, skin prick testing results), allergy medications, and established pancreas cancer risk factors. Logistic regression was used to estimate odd ratios and test potential confounders, including allergy medications. Hay fever was associated with a significant reduction in pancreatic cancer risk [AOR = 0.68; 95% confidence intervals (CI), 0.52-0.89], and reduction was greatest for those whose skin prick test was positive for hay fever allergens. No particular patterns were observed as regards age at onset and duration of allergy. Positive dust/mold allergy skin prick test and animal allergies were associated with a statistically significant reduced pancreatic cancer risk; AOR = 0.49; 95% CI, 0.31-0.78 and AOR = 0.68; 95% CI, 0.46-0.99, respectively. Asthma was not associated with pancreatic cancer risk. These findings support the growing body of evidence that suggests certain allergies are associated with reduced pancreatic cancer risk.

Dietary Patterns and Risk of Pancreatic Cancer in a Large Population-Based Case-Control Study in the San Francisco Bay Area

Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A prudent dietary pattern, characterized by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men [odds ratio (OR) = 0.51, 95% confidence intervals (CI) = 0.31–0.84, P trend = 0.001] and women (OR = 0.51, 95% CI = 0.29–0.90, P trend = 0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined grains, was associated with a 2.4-fold increased risk of pancreatic cancer among men (95% CI = 1.3–4.2, P trend = 0.008) but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the prudent diet had a threefold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer.

The Associations of Advanced Glycation End Products and Its Soluble Receptor with Pancreatic Cancer Risk: A Case–Control Study within the Prospective EPIC Cohort

Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P(interaction) = 0.002). Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations.

The association of circulating adiponectin levels with pancreatic cancer risk: A study within the prospective EPIC cohort

Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development.

Can physical activity modulate pancreatic cancer risk? a systematic review and meta‐analysis

Numerous epidemiological studies have examined the association between physical activity and pancreatic cancer; however, findings from individual cohorts have largely not corroborated a protective effect. Among other plausible mechanisms, physical activity may reduce abdominal fat depots inducing metabolic improvements in glucose tolerance and insulin sensitivity, thereby potentially attenuating pancreatic cancer risk. We performed a systematic review to examine associations between physical activity and pancreatic cancer. Six electronic databases were searched from their inception through July 2009, including MEDLINE and EMBASE, seeking observational studies examining any physical activity measure with pancreatic cancer incidence/mortality as an outcome. A random effects model was used to pool individual effect estimates evaluating highest vs. lowest categories of activity. Twenty-eight studies were included. Pooled estimates indicated a reduction in pancreatic cancer risk with higher levels of total (five prospective studies, RR: 0.72, 95% CI: 0.52-0.99) and occupational activity (four prospective studies, RR: 0.75, 95% CI: 0.59-0.96). Nonsignificant inverse associations were seen between risks and recreational and transport physical activity. When examining exercise intensity, moderate activity appeared more protective (RR: 0.79, 95% CI: 0.52-1.20) than vigorous activity (RR: 0.97, 95% CI: 0.85-1.11), but results were not statistically significant and the former activity variable incorporated marked heterogeneity. Despite indications of an inverse relationship with higher levels of work and total activity, there was little evidence of such associations with recreational and other activity exposures.

Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies

Background:Studies evaluating vitamin D status in relation to pancreatic cancer risk have yielded inconsistent results.Methods:We prospectively followed 118 597 participants in the Nurses' Health Study and Health Professionals Follow-up Study from 1986 to 2006. We calculated a 25-hydroxyvitamin D (25(OH)D) score from known predictors of vitamin D status for each individual and then examined the predicted 25(OH)D levels in relation to pancreatic cancer risk. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models adjusted for age, sex, race, height, smoking, and diabetes. We then further adjusted for body mass index (BMI) and physical activity in a sensitivity analysis.Results:During 20 years of follow-up, we identified 575 incident pancreatic cancer cases. Higher 25(OH)D score was associated with a significant reduction in pancreatic cancer risk; compared with the lowest quintile, participants in the highest quintile of 25(OH)D score had an adjusted RR of 0.65 (95% CI=0.50–0.86; Ptrend=0.001). Results were similar when we further adjusted for BMI and physical activity.Conclusions:Higher 25(OH)D score was associated with a lower risk of pancreatic cancer in these two prospective cohort studies.

Abstract A107: Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies

Abstract Background: Experimental data indicate that vitamin D has anticancer properties. However, epidemiologic studies on vitamin D and pancreatic cancer risk have yielded inconsistent results. We previously developed a model to predict long-term plasma 25-hydroxyvitamin D3 [25(OH)D] levels from multiple determinants of vitamin D status (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic residence, and leisure-time physical activity as a surrogate of sunlight exposure). Here, we examine the association between predicted vitamin D status and pancreatic cancer risk in the Nurses' Health Study and Health Professionals Follow-up Study. Methods: We prospectively followed 118,597 participants in these two cohorts from 1986–2006. We calculated a 25(OH)D score from six predictors of vitamin D status for each individual using a multiple linear regression model and then examined the predicted 25(OH)D levels in relation to pancreatic cancer risk with Cox proportional hazards models. The multivariate models were adjusted for age, sex, race, height, smoking, and diabetes. Results: During 20 years of follow-up, we identified 575 incident pancreatic cancer cases. Higher 25(OH)D score was associated with a significant reduction in pancreatic cancer risk; compared with the lowest quintile, participants in the highest quintile of 25(OH)D score had an adjusted RR of 0.65 (95% CI, 0.50–0.86; P for trend = 0.001). The results remained unchanged after further adjusting for BMI and physical activity or after excluding the first 2 years of follow-up. This inverse association was also consistent across gender and strata of other covariates, including age, region, smoking, BMI, and physical activity. Conclusion: Higher 25(OH)D score was associated with a lower risk of pancreatic cancer in these two prospective cohort studies. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A107.

Dietary Intake of Lycopene Is Associated with Reduced Pancreatic Cancer Risk

Although fruits and vegetables have been implicated in the etiology of pancreatic cancer, the role of phytochemicals in these food groups has received little attention to date. In this study, we investigated the possible association between dietary carotenoids and pancreatic cancer risk. A case-control study of 462 histologically confirmed pancreatic cancer cases and 4721 population-based controls in 8 Canadian provinces took place between 1994 and 1997. Dietary intake was assessed by a self-administered FFQ. Unconditional logistic regression was used to assess associations between specific and total carotenoid intakes and the risk of pancreatic cancer. All tests of statistical significance were 2-sided. After adjustment for age, province, BMI, smoking, educational attainment, dietary folate, and total energy intake, lycopene, provided mainly by tomatoes, was associated with a 31% reduction in pancreatic cancer risk among men [odds ratio (OR) = 0.69; 95% CI: 0.46–0.96; P = 0.026 for trend] when comparing the highest and lowest quartiles of intake. Both β-carotene (OR = 0.57; 95% CI: 0.32–0.99; P = 0.016 for trend) and total carotenoids (OR = 0.58; 95% CI: 0.34–1.00; P = 0.02 for trend) were associated with a significantly reduced risk among those who never smoked. The results of this study suggest that a diet rich in tomatoes and tomato-based products with high lycopene content may help reduce pancreatic cancer risk.

A Prospective Study of Cigarette Smoking and the Risk of Pancreatic Cancer

To prospectively examine the excess incidence of pancreatic cancer among cigarette smokers and to examine the influence of smoking cessation on the risk of pancreatic cancer. We obtained data on cigarette smoking and other risk factors for pancreatic cancer from 118,339 women aged 30 to 55 years and 49,428 men aged 40 to 75 years who were without diagnosed cancer. During the 2,116,229 persons-years of follow-up, pancreatic cancer was diagnosed in 186 participants. The multivariate relative risk of pancreatic cancer for current smokers was 2.5 (95% confidence interval, 1.7-3.6). A significant, positive trend in risk with increasing pack-years of smoking was observed (P for trend = .004), although this association was confined to cigarette consumption within the past 15 years. Compared with participants who continued to smoke, former smokers had a 48% reduction in pancreatic cancer risk within 2 years of quitting. Ultimately, the relative risk of pancreatic cancer among former smokers approached that for never smokers after less than 10 years of smoking cessation. Overall, the proportion of pancreatic cancers attributable to cigarette smoking was 25%. Cigarette smoking is associated with an increased risk of pancreatic cancer. The rapid reduction in risk associated with quitting suggests that smoking cessation could eliminate 25% of the 27,000 deaths from pancreatic cancer occurring annually in the United States.

Early precursors of pancreatic cancer in college men

From college data on 50,000 male former students, the records of 126 men who died of pancreatic cancer in a 16–50yr follow-up period were compared with those of 504 surviving classmates with respect to physical and social characteristics. Return mail questionnaires received from 30,000 surviving alumni in 1962 or 1966 also were reviewed for characteristics that might predict altered risk of pancreatic cancer. Strong positive associations were found for cigarette smoking as reported both during college ( p < 0.001) and at time of questionnaire return ( p = 0.03). Smoking 10 or more cigarettes per day during college corresponded to a relative risk of 2.6 with 95% confidence limits 1.5 to 4.6, and a positive smoking history at questionnaire return yielded a relative risk of 2.4 (1.1–5.1). No association was found for collegiate coffee drinking, either before or after adjustment for cigarette smoking. The relative risk for coffee drinking adjusted for smoking was 1.1 (0.7–1.8). In contrast, collegiate tea consumption was associated with a reduction in pancreatic cancer risk. The relative risk for tea drinking adjusted for smoking was 0.5 (0.3–0.9). Men who at college physical examination complained of occasional abdominal pain or discomfort had increased relative risk of pancreatic cancer (3.1 ; 1.1–9.0) in the follow-up period.