On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer

Although it has been suggested that dietary energy intake restriction may be related to reduced BRCA-associated breast cancer (BC) risk, it is currently not known whether overall diet quality could predict the BC risk among women with deleterious mutations in BRCA1 and BRCA2 (BRCA) genes who already have an elevated BC risk. To assess possible relationships between diet quality, reflected by the Alternate Healthy Eating Index (AHEI), the Diet Quality Index-Revised (DQI-R), the alternate Mediterranean Diet Index (aMED), the Canadian Healthy Eating Index (CHEI), and BRCA-associated BC risk, a case-control study was carried out within a cohort of 80 French-Canadian families with 250 members involving 89 carriers of BRCA genes affected by BC, 48 non-affected carriers and 46 non-affected non-carriers. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in unconditional logistic regression models. After adjustment for age, physical activity and total energy intake, we did not detect any association between the AHEI or aMED and BC. However, a strong and significant inverse relationship was apparent between the DQI-R and CHEI and BRCA-associated BC risk. ORs comparing the highest and lowest tertiles of diet quality scores were 0.35 (95%CI = 0.12–1.02; p = 0.034 for trend) for the DQI-R and 0.18 (95%CI = 0.05–0.68; p = 0.006 for trend) for the CHEI, respectively. These inverse associations were not the result of a link with any specific component of the diet quality indexes. These results suggest that dietary guidelines reflected by the DQI-R and CHEI may constitute preventive strategies for reducing BRCA-associated BC risk.     

Breast cancer risk in relation to the joint effect of BRCA mutations and diet diversity

It has been suggested that gene–environment interaction is related to the risk of cancer. To evaluate departure from multiplicative effects between BRCA mutations and diet diversity in breast cancer (BC), a case-only study was carried out in a French-Canadian population including 738 patients with incident primary BC comprising 38 BRCA mutation carriers. Diet diversity was assessed using a validated food frequency questionnaire. Unconditional logistic regression analysis was performed to assess case-only odds ratio (COR) and 95% confidence interval (CI) while adjusting for age, body mass index, smoking, hormonal replacement therapy, and total energy intake. Ours results reveal a strong and significant interaction between BRCA mutations and vegetable and fruit diversity (COR = 0.27; 95%CI = 0.10–0.80; P = 0.03) when comparing the upper to the lower quartiles. The estimates for departure from multiplicative effects between BRCA mutations and total or other food groups’ diversity were not supportive of the idea of a gene–environment interaction. The results of this study suggest that the combination of BRCA mutations and vegetable and fruit diversity may be associated with a reduced risk of BC.     

The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers

Tobacco smoke is an established carcinogen, but the association between tobacco smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this study was to evaluate prospectively the association between tobacco smoking and cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study population consisted of unaffected BRCA mutation carriers. Information on lifestyle including smoking histories, reproductive factors, and past medical histories was obtained through questionnaires. Incident cancers were updated biennially via follow‐up questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using time‐dependent Cox regression models. There were 700 incident cancers diagnosed over 26,711 person‐years of follow‐up. The most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%) and ovarian (n = 109; 15%) cancer. Compared to nonsmokers, (ever) smoking was associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI 1.01–1.37). Women in the highest group of total pack‐years (4.3–9.8) had an increased risk of developing any cancer (HR = 1.27; 95%CI 1.04–1.56), breast cancer (HR = 1.33, 95%CI 1.02–1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06–2.67) compared to never smokers. The associations between tobacco smoking and cancer did not differ by BRCA mutation type or by age at diagnosis. This prospective study suggests that tobacco smoking is associated with a modest increase in the risks of breast and ovarian cancer among women with BRCA1 or BRCA2 mutation.     

Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA‐associated ovarian cancer. Thus, we conducted a matched case–control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41–0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48–0.79) and 50% (95% CI 0.29–0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40–0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22–0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79–0.96; p‐trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81–1.19; p‐trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03–1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.     

Lifestyle Characteristics in Women Carriers of BRCA Mutations: Results From an Italian Trial Cohort

BackgroundWomen with deleterious mutations in BRCA1/2 have a high lifetime penetrance of developing breast cancer and/or ovarian cancer. Genetic and/or environmental factors may influence BRCA penetrance, and identifying modifiable exposures might be valuable for prevention.Patients and MethodsWe implemented a multicenter prospective 2-arm (1:1) randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction would reduce potential modulators of BRCA penetrance such as insulin-like growth factor 1 (IGF-1), body weight, and metabolic risk factors. We studied the baseline characteristics of women with BRCA-positive disease who joined the trial cohort, focusing on the relationships between selected lifestyle exposures, metabolic/anthropometric parameters, and BRCA-related cancer.ResultsA total of 502 women (304 with a previous diagnosis of breast cancer and/or ovarian cancer and 198 unaffected) with deleterious BRCA mutations, with or without a previous cancer, aged 18 to 70 years and without metastases were included. Late age at menarche and pregnancy were negatively associated with BRCA-related cancer, especially in women with BRCA1-positive disease. Higher fat mass and the presence of 4 or 5 metabolic risk factors were significantly associated with BRCA-related cancer (hazard ratio, 1.87, 95% confidence interval, 1.21-2.88; and hazard ratio, 1.87, 95% confidence interval, 1.11-3.19, respectively), with greater effect in BRCA2-positive women.ConclusionsOur findings confirm previous observations about reproductive factors in women with BRCA disease and suggest a potential impact of metabolic factors in BRCA-related cancer. The prospective follow-up of the trial cohort will enable us to study the environmental modulators of BRCA penetrance and their impact in relation to the history of BRCA-related cancer. [ClinicalTrials.gov NCT03066856]     

No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study

Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92–1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81–1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers.     

Adolescent dietary phytoestrogen intake and breast cancer risk (Canada)

Objective It has been suggested that dietary phytoestrogen intake during adolescence may reduce the risk of developing breast cancer. This population-based case–control study evaluated the association between adolescent dietary phytoestrogen intake and adult breast cancer risk among women in Ontario, Canada. Methods Pathology-confirmed, population-based breast cancer cases, aged 25–74 years, diagnosed between June 2002 and April 2003, were identified using the Ontario Cancer Registry. Population-based controls were recruited, and matched to cases within 5-year age groups. Adolescent phytoestrogen intake was obtained using a brief food frequency questionnaire (n = 3,024 cases, n = 3,420 controls). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Higher phytoestrogen intake (both isoflavones and lignans) during adolescence was associated with a reduced breast cancer risk, and a monotonic trend was observed from the lowest to the highest quartile (OR [Q2] = 0.91, 95% CI 0.79–1.04, OR[Q3] = 0.86, 95% CI 0.75–0.98, and OR[Q4] = 0.71, 95% CI 0.62–0.82, p-trend < 0.001). Conclusion Adolescent dietary phytoestrogen intake may be associated with a decreased risk of adult breast cancer. If verified, this finding has important implications with regard to breast cancer prevention since diet is a potentially modifiable factor.     

Survival improvement in hormone-responsive young breast cancer patients with endocrine therapy

Purpose

Breast cancer (BC) is the most frequent cancer among women in developed countries. Physical activity (PA), body mass index (BMI), and alcohol intake have been identified as relevant lifestyle modifiable risk factors for post-menopausal BC. We aimed to evaluate the role of these factors in modulating post-menopausal BC risk and to estimate the proportion of BC cases attributable to low PA, high BMI, and alcohol taking into account non-modifiable factors.

Methods

In the Italian section of the EPIC study, 15,010 post-menopausal women were recruited and provided information about dietary and lifestyle habits including PA, smoking, reproductive history, and anthropometric measurements. During 14.8 years of median follow-up, 672 incident BC cases (607 invasive and 65 in situ) were identified.

Results

In multivariate models, inverse associations with BC risk emerged for increasing level of total (p trend 0.02), leisure time (p trend 0.04), and occupational (p trend 0.007) PA. High BMI (HR 1.21; 95% CI 1.02–1.43 and HR 1.33; 95% CI 1.06–1.65 for overweight and obesity, respectively) and alcohol consumption higher than 10 g/day (HR 1.30; 95% CI 1.09–1.54) were associated with BC risk. We estimated that 30% (95% CI 8–50%) of post-menopausal BC cases would be avoided through an increase of leisure time PA, a BMI below 25.0, and consuming no more than one drink/day.

Conclusions

This large study carried out in Mediterranean women confirms the role of PA, BMI, and alcohol consumption in modulating post-menopausal BC risk and supports the potential benefits obtainable by modifying these lifestyle factors.

     

Risk of metachronous breast cancer after BRCA mutation–associated ovarian cancer

BACKGROUND:

This study sought to estimate the risk of breast cancer (BC) after a diagnosis of ovarian cancer (OC) associated with mutation of the BRCA1/2 (breast cancer, early onset) genes (BRCA‐OC).

METHODS:

The Memorial Sloan‐Kettering Cancer Center and the University of Pennsylvania, clinical genetics databases were searched to identify women with BRCA‐OC who participated in genetic testing and follow‐up studies from 1995 to 2009. The primary objective was to determine the risk of developing BC after BRCA‐OC. Overall survival (OS) and BC‐free survival (BCFS) were determined by the Kaplan‐Meier method; patients were censored at the time of last follow‐up.

RESULTS:

A total of 164 patients had BRCA‐OC (115 with BRCA1; 49 with BRCA2). Of these 164 patients, 152 developed OC prior to BRCA testing (median time to testing, 2.4 years [0.01‐55 years]). Median follow‐up from OC for those not developing BC was 5.8 years (0.25‐55.6 years). There were 46 deaths, but none were due to BC. The 5‐ and 10‐year OS were 85% (95% confidence interval [CI] = 0.78, 0.90) and 68% (95% CI = 0.59, 0.76), respectively. There were 18 metachronous BC diagnoses. The 5‐ and 10‐year BCFS were 97% (95% CI = 0.92, 0.99) and 91% (95% CI = 0.82, 0.95), respectively. A subset of 64 women were tested either before or within 12 months of BRCA‐OC. In this pseudo‐incident subset, 5‐ and 10‐ year OS was 71% (95% CI = 0.53, 0.83) and 62% (95% CI = 0.44, 0.75), respectively, and 5‐ and 10‐year BCFS were 100% and 87% (95% CI = 0.56, 0.96), respectively.

CONCLUSIONS:

OS was dominated by OC deaths. Metachronous BC risk was lower than reported for unaffected BRCA mutation carriers. These results support nonsurgical management of BC risk in women with BRCA‐OC. Cancer 2013. © 2012 American Cancer Society.     

IGFBP1 and IGFBP3 polymorphisms predict circulating IGFBP-3 levels among women from high-risk breast cancer families

The insulin-like growth factor (IGF) pathway has been implicated as risk modifier in premenopausal breast cancer. In this study, associations between single nucleotide polymorphisms (SNPs) and diplotypes in the IGFBP1 and IGFBP3 genes and circulating IGFBP-3 levels, BRCA family status and breast cancer among women from high-risk breast cancer families were investigated. Nine IGFBP1 and IGFBP3 SNPs were genotyped with PCR-based methods in 323 women. Nine IGFBP1 and ten IGFBP3 diplotypes were identified. Plasma IGFBP-3 levels obtained during cycle day 18–23 were available for 231 women, 87 current users of combined oral contraceptives and 144 non-users. IGFBP1 (rs1995051 and rs4988515) and IGFBP3 (rs2471551 and rs2854744) SNPs were associated with circulating IGFBP-3 levels (P < 0.05). IGFBP1 ^low diplotypes were associated with lower IGFBP-3 levels and were more common in BRCA2 families OR 2.05 (95%CI 0.97–4.30). IGFBP3 ^high diplotypes were associated with higher IGFBP-3 levels and were more common in BRCAX families OR 1.68 (95%CI 1.04–2.74). After adjusting the models for BRCA family status, both the BRCA1 and BRCA2 family status (P ≤ 0.006) and the IGFBP1 diplotype GTAC/ACAT (P = 0.004) were associated with lower IGFBP-3 levels. Similarly, both the BRCA1 and BRCA2 family status (P ≤ 0.03) and the IGFBP-3 diplotypes GCA/GCG (P = 0.007) and GCG/CCG (P = 0.002) were significantly associated with lower IGFBP-3 levels, adjusted for age, weight, OC use, and other IGFBP diplotypes. No individual SNP was associated with breast cancer. There were 23 cases of breast cancer and one IGFBP1 diplotype was associated with a decreased risk of breast cancer after age 18 (log rank P=0.05). In conclusion, independent effects from IGFBP1, IGFBP3 diplotypes, and BRCA family status on IGFBP-3 levels were observed. These factors may influence the risk of breast cancer among women from high-risk breast cancer families.     

Glycemic index, carbohydrate and fiber intakes and risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma

Objective  To examine the association between dietary glycemic index (GI), glycemic load (GL), total carbohydrate, sugars, starch, and fiber intakes and the risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Methods  In an all-Ireland study, dietary information was collected from patients with esophageal adenocarcinoma (n = 224), long-segment Barrett’s esophagus (n = 220), reflux esophagitis (n = 219), and population-based controls (n = 256). Multiple logistic regression analysis examined the association between dietary variables and disease risk by tertiles of intake and as continuous variables, while adjusting for potential confounders. Results  Reflux esophagitis risk was positively associated with starch intake and negatively associated with sugar intake. Barrett’s esophagus risk was significantly reduced in people in the highest versus the lowest tertile of fiber intake (OR 0.44 95%CI 0.25–0.80). Fiber intake was also associated with a reduced risk of esophageal adenocarcinoma, as was total carbohydrate intake (OR 0.45 95%CI 0.33–0.61 per 50 g/d increase). However, an increased esophageal adenocarcinoma risk was detected per 10 unit increase in GI intake (OR 1.42 95%CI 1.07–1.89). Conclusions  Our findings suggest that fiber intake is inversely associated with Barrett’s esophagus and esophageal adenocarcinoma risk. Esophageal adenocarcinoma risk is inversely associated with total carbohydrate consumption but positively associated with high GI intakes.     

Intake of fruits, and vegetables in relation to breast cancer risk by hormone receptor status

Summary The inconsistent associations between fruit and vegetable intake and breast cancer risk may be due to heterogeneity of associations by estrogen (ER) and progesterone receptor (PR) status of the tumors. We evaluated this hypothesis in a large (2,386 cases and 2,503 controls) population-based case-control study in Poland, conducted between 2000 and 2003. We observed significant associations between reduced overall risk of breast cancer and increasing levels of total fruit intake (odds ratio (OR) for highest versus lowest quartile = 0.76, 95%CI = 0.63–0.91; p-trend = 0.01), but not for total vegetable intake (1.13 (0.93–1.37), p-trend = 0.25), after controlling for age, energy intake and known risk factors for breast cancer. The inverse association with total fruit intake was stronger for risk of ER+ (0.69 (0.54–0.88), p-trend = 0.01) than ER− tumors (0.89 (0.67–1.19), p-trend = 0.57) (p-heterogeneity = 0.02). In conclusion, this study suggests that fruit intake might have differential associations for breast tumor subtypes defined by ER status.     

Evaluation of the BOADICEA risk assessment model in women with a family history of breast cancer

The ability of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model to predict BRCA1 and BRCA2 mutations and breast cancer incidence in women with a family history of breast cancer was evaluated. Observed mutations in 263 screened families were compared to retrospective predictions. Similarly, observed breast cancers in 640 women were compared to retrospective predictions of breast cancer incidence. The ratios of observed to expected number of BRCA1- , BRCA2- and BRCA(1 or 2) mutations were 1.43 (95% CI 1.05–1.90), 0.63 (95% CI 0.34–1.08), and 1.12 (95% CI 0.86–1.44), showing a significant underestimation of BRCA1 mutations. Discrimination between carriers and non-carriers as measured by area under the receiver operating characteristic (ROC) curve was 0.83 (95% CI 0.76–0.88). The ratio of observed to expected number of invasive breast cancers was 1.41 (0.91–2.08). The corresponding area under the ROC curve for prediction of invasive breast cancer at individual level was 0.62 (95% CI 0.52–0.73). In conclusion, the BOADICEA model can predict the total prevalence of BRCA(1 or 2) mutations and the incidence of invasive breast cancers. The mutation probability as generated by BOADICEA can be used clinically as a guideline for screening, and thus decrease the proportion of negative mutation analyses. Likewise, individual breast cancer risks can be used for selecting women whose risk of breast cancer indicates follow-up. Application of local mutation frequencies of BRCA1 and BRCA2 could improve the ability to distinguish between the two genes.     

Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai women's health study

Nitrate and nitrite are precursors in the endogenous formation of N‐nitroso compounds and nitrate can disrupt thyroid homeostasis by inhibiting iodide uptake. We evaluated nitrate and nitrite intake and risk of thyroid cancer in the Shanghai Women's Health Study that included 73,317 women, aged 40–70 years enrolled in 1996–2000. Dietary intake was assessed at baseline using a food frequency questionnaire. During approximately 11 years of follow‐up, 164 incident thyroid cancer cases with complete dietary information were identified. We used Cox proportional hazards regression to estimate relative risks (RRs). We determined the nitrate and nitrite contents of foods using values from the published literature and focusing on regional values for Chinese foods. Nitrate intake was not associated with thyroid cancer risk [RR_Q4 = 0.93; 95% confidence interval (CI): 0.42–2.07; p for trend = 0.40]. Compared to the lowest quartile, women with the highest dietary nitrite intake had about a twofold risk of thyroid cancer (RR_Q4 = 2.05; 95%CI: 1.20–3.51), but there was not a monotonic trend with increasing intake (p for trend = 0.36). The trend with increasing nitrite intake from animal sources was significant (p for trend = 0.02) and was stronger for nitrite from processed meats (RR_Q4 = 1.96; 95%CI: 1.28–2.99; p for trend < 0.01). Although we did not observe an association for nitrate as hypothesized, our results suggest that women consuming higher levels of nitrite from animal sources, particularly from processed meat, may have an increased risk of thyroid cancer.     

Glycemic Load,Glycemic Index,and the Risk of Breast Cancer Among Mexican Women

Objective: The amount and composition of dietary carbohydrates is a major determinant of postprandial blood glucose and insulin, and risk of breast cancer has been positively associated with plasma levels of insulin and insulin-like growth factor 1. We sought to evaluate dietary glycemic load (GL) and overall glycemic index (GI) in relation to breast cancer risk in Mexican women. Methods: We examined dietary GL and overall GI and breast cancer risk among 475 women with histologically-confirmed breast cancer and a random sample of 1391 women from Mexico City households. Diet was assessed using a food frequency questionnaire adapted to the Mexican population. Results: The multivariate adjusted or for all women comparing the highest quartile of dietary GL with the lowest quartile was 1.62 (95% CI 1.13–2.32; p-test for trend = 0.02) with a significant trend. In postmenopausal women, the multivariate adjusted or comparing the extreme quartiles was 2.18 (95% CI 1.34–3.55; p-test for trend=0.005). Overall GI was not significantly associated with risk of breast cancer. Conclusion: High intake of rapidly absorbed carbohydrate appears to play an important role in the risk of breast cancer in Mexican women.     

Dietary risk factors for ovarian cancer: the Adventist Health Study (United States)

Few prospective studies have reported dietary risk factors for ovarian cancer. A total of 71 histologically confirmed epithelial ovarian cancers occurred among 13,281 non-Hispanic white California Seventh-day Adventist women during follow-up. Participants were part of the Adventist Health Study (AHS) and had no history of cancer or hysterectomy at baseline in 1976 when they completed a detailed lifestyle questionnaire including a dietary assessment. The association of dietary variables with either all ovarian cancer cases or postmenopausal cases was tested using proportional hazards regression with adjustment for age and other covariates. The strongest hazardous risk factor associations among the food variables were found for meat intake with a risk ratio (RR) of 2.42 for intake ≥1 time/week versus no meat (p for trend = 0.006), and cheese intake with a RR of 2.02 for intake of >2 time/week versus <1 per week (p for trend = 0.10), both of these being in postmenopausal cases. We found significantly reduced risk of all ovarian cancer with higher tomato consumption (RR = 0.32) comparing intakes ≥ five times/week versus never to <1 time/week (p for trend = 0.002), and also with higher fruit consumption (p < 0.01). A weak protective association was found with low fat, but not whole milk. Little confounding was observed between these foods.     

Anthropometric Factors and Pancreatic Cancer in a Population-based Case–control Study in the San Francisco Bay Area

Objective: To investigate the association between pancreatic cancer, anthropometric factors, physical activity and caloric intake. Methods: Participants in our population-based case–control study of adenocarcinoma of the exocrine pancreas (532 cases, 1701 frequency-matched controls) in the San Francisco Bay Area were accrued between 1995 and 1999 and interviewed in-person. Data were analyzed by sex in age-adjusted unconditional logistic models and main effects were considered significant for two-sided p-values ≤ 0.05. Results: Odds ratios were elevated for body mass index (BMI) at age 25 years (4th versus 1st quartile: odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.4–3.1), maximum BMI (OR = 1.8, 95% CI: 1.2–2.7) and usual adult BMI (OR = 2.1, 95% CI: 1.4–3.2) among men. Odds ratios were elevated for increased caloric intake among men (4th versus 1st quartile: OR = 2.6, 95% C: 1.7–3.8). Increased physical activity was suggestive of decreased risk in men and women although CIs included unity. Our results suggest that increased BMI and caloric intake are associated with pancreatic cancer among men. Conclusions: These results are consistent with other cancer studies and support further research to determine the mechanism by which increased BMI may influence the development of pancreatic cancer.     

Diet,physical activity,and body size associations with rectal tumor mutations and epigenetic changes

Diet and lifestyle factors have been inconsistently associated with rectal tumors. It is possible that evaluation of specific tumor markers with these factors may help clarify these associations. In this study, we examine energy contributing nutrients, dietary fiber, BMI (kg/m2), and long-term physical activity with TP53 mutations, KRAS2 mutations, and CpG Island Methylator Phenotype (CIMP) in 750 population-based cases of rectal cancer compared to healthy controls. We observed that high levels of physical activity reduced the risk of having TP53 and KRAS2 rectal tumor mutations. Dairy products rich in fat were associated with an increased risk of CIMP+ tumors (OR 1.88 95% CI 0.92, 3.84), while low-fat dairy products reduced risk of CIMP+ tumors (OR 0.56 95% CI 0.29, 1.09). Omega-3 fatty acids were associated with a twofold increased risk of a CIMP+ tumor. High levels of vegetable intake reduced risk of both TP53 mutations (OR 0.73 95% CI 0.54, 1.00; p trend 0.02) and KRAS2 mutations (OR 0.60 95% CI 0.40, 0.89; p trend <0.01). High intake of whole grains reduced the likelihood of a TP53 mutation (OR 0.74 95% CI 0.56, 0.99), while high intake of refined grains increased the likelihood of a TP53 mutation (OR 1.41 95% CI 1.02, 1.96). Dietary fiber also was associated with reduced risk of TP53 and KRAS2 rectal tumor mutations. Overall, a prudent dietary pattern significantly reduced the likelihood of a KRAS2 tumor mutation (OR 0.68 95% CI 0.47, 0.98; p linear trend 0.03). These data suggest that diet and lifestyle factors are associated with specific types of rectal tumor mutations and epigenetic changes. Findings need confirmation in other studies.