Serologic markers of viral infection and risk of non‐Hodgkin lymphoma: A pooled study of three prospective cohorts in China and Singapore

Incidence rates of non‐Hodgkin lymphoma (NHL) and distributions of certain viruses differ between East Asian and Western populations. There are limited data on associations between serologic markers of multiple viral infections in pre‐diagnostic blood and NHL risk in East Asians. We conducted a nested case‐control study of 214 NHL cases and 214 matched controls from three population‐based prospective cohorts in Shanghai and Singapore. Antibodies against antigens from herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were measured in plasma or serum using fluorescent bead‐based multiplex assays. Conditional logistic regression was used to evaluate associations between antibody levels and NHL risk. An increased risk of NHL was observed for higher compared to lower EA‐D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) = 1.10‐3.81; p_trend = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96‐4.89; p_trend = 0.008) Epstein‐Barr Virus (EBV) antibodies, as well as for antibody seropositivity against the IE1A human herpesvirus‐6 (HHV‐6) antigen (OR = 1.85, 95% CI = 1.04‐3.29). An increased NHL risk was also observed for higher compared to lower antibodies against the HBV‐HBc and HBe antigens. An increased risk of NHL in relation to EBV and HBV infection in East Asians is consistent with findings in several studies of Western populations, suggesting similar viral risk factors for NHL in these diverse populations with distinct patterns of NHL. The association between HHV‐6 antibodies and NHL has not previously been reported in a prospective study in this population and will require replication.     

Intake of fatty acids and antioxidants and pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area

There are no well‐established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all p_trend < 0.01), monounsaturated palmitoleic and oleic fatty acids [OR = 1.6 (95% CI: 1.2–2.1) and 1.4 (95% CI: 1.1–1.9); both p_trend < 0.01], and polyunsaturated linolenic acid [OR = 1.5 (95% CI: 1.1–2.0); p_trend = 0.02]. Inverse associations were observed for high levels of gadolic acid [4th vs. 1st quartile: OR = 0.68 (95% CI: 0.50–0.92); p_trend = 0.007] and omega‐3 fatty acids [≥0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25–0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51–0.94); p_trend = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49–0.92); p_trend = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both p_trend < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega‐3 fatty acids, vitamins C and E may reduce the risk.     

A prospective study of dairy product intake and the risk of hepatocellular carcinoma in U.S. men and women

Although increasing dairy product intake has been associated with risk of several cancers, epidemiological studies on hepatocellular carcinoma are sparse and have yielded inconsistent results. We prospectively assessed the associations of dairy products (total, milk, butter, cheese and yogurt) and their major components (calcium, vitamin D, fats and protein) with the risk of hepatocellular carcinoma development among 51,418 men and 93,427 women in the Health Professionals Follow-Up Study and the Nurses' Health Study. Diets were collected at baseline and updated every 4 years using validated food frequency questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression model. During up to 32 years of follow-up, a total of 164 hepatocellular carcinoma cases were documented. After adjustment for most known hepatocellular carcinoma risk factors, higher total dairy product intake was associated with an increased risk of hepatocellular carcinoma (highest vs. lowest tertile, HR = 1.85, 95% CI: 1.19–2.88; p_trend = 0.009). For the same comparison, we observed significant positive associations of high-fat dairy (HR = 1.81, 95% CI: 1.19–2.76; p_trend = 0.008) and butter (HR = 1.58, 95% CI: 1.06–2.36; p_trend = 0.04) with hepatocellular carcinoma risk. There was a nonsignificant inverse association between yogurt intake and hepatocellular carcinoma risk (HR = 0.72, 95% CI: 0.49–1.05; p_trend = 0.26). Our data suggest that higher intake of high-fat dairy foods was associated with higher, whereas higher yogurt consumption might be associated with lower risk of developing hepatocellular carcinoma among U.S. men and women.     

Isothiocyanates,glutathione S‐transferase M1 and T1 polymorphisms and gastric cancer risk: A prospective study of men in Shanghai,China

Isothiocyanates (ITC) in cruciferous vegetables may be chemopreventive against gastric cancer development. Glutathione S‐transferases (GSTs) may modify the chemopreventive effect of ITC. The relationship between urinary total ITC and risk of gastric cancer was prospectively examined. Between 1986 and 1989, 18,244 middle‐aged men in Shanghai, China were enrolled in a prospective study of diet and cancer and donated baseline urine and blood samples. Urinary ITC was quantified for 307 incident cases of gastric cancer that occurred during the first 16 years of follow‐up, and 911 matched control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression methods. Seropositivity for antibodies to Helicobacter pylori and homozygous deletions of GSTM1 and GSTT1 were determined. Compared to the first tertile, ORs (95% CIs) of gastric cancer for the second and third tertiles of urinary total ITC were 0.83 (0.61–1.15) and 0.66 (0.47–0.94) (p_trend = 0.02). A stronger protective effect of ITC against gastric cancer development was seen among men with homozygous deletion of GSTM1 (third tertile versus first tertile, OR = 0.50, 95% CI = 0.27–0.93) or GSTT1 (third tertile vs. first tertile, OR = 0.47, 95% CI = 0.25–0.88), and particularly with deletions of both GSTM1 and GSTT1 (second and third tertiles vs. first tertile, OR = 0.44, 95% CI = 0.21–0.93). In this cohort of Chinese men at high risk for gastric cancer, isothiocyanates may protect against the development of gastric cancer. The protection may be stronger for individuals genetically deficient in enzymes that metabolize these chemopreventive compounds. © 2009 UICC     

Magnesium intake and primary liver cancer incidence and mortality in the Prostate,Lung, Colorectal and Ovarian Cancer Screening Trial

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratio_{tertile 3 vs. 1}: 0.44; 95% confidence interval: 0.24, 0.80; p_trend = 0.0065) and mortality (subdistribution hazard ratio_{tertile 3 vs. 1}: 0.37; 95% confidence interval: 0.19, 0.71; p_trend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose–response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all p_nonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose–response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.     

Circulating anti‐Müllerian hormone and breast cancer risk: A study in ten prospective cohorts

A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (p_trend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (p_interaction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: OR_Q4–Q1 = 1.96, 95% CI = 1.46–2.64, p_trend <0.0001; ER+/PR?: OR_Q4–Q1 = 0.82, 95% CI = 0.40–1.68, p_trend = 0.51; ER?/PR+: OR_Q4–Q1 = 3.23, 95% CI = 0.48–21.9, p_trend = 0.26; ER?/PR?: OR_Q4–Q1 = 1.15, 95% CI = 0.63–2.09, p_trend = 0.60. The association was observed for both pre‐ (OR_Q4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (OR_Q4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (p_interaction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.     

Alcohol intake and risk of non-Hodgkin lymphoma in men and women

Objective: The effect of alcohol intake on risk of NHL is unclear. We therefore conducted a population-based case-control study to examine the association between alcohol and NHL risk. Methods: 613 NHL cases and 480 population controls in Sweden reported their average consumption of beer, wine, and liquor 2years before the study. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) for associations between alcohol intake and NHL risk. Results: Intake of total alcohol, beer, wine, or liquor was not associated with risk of overall NHL. There was no difference in risk of NHL among those who habitually consumed above 19.1g of ethanol per day, compared to those who consumed on average 0–2.2g of ethanol per day (OR = 1.2 (95% CI: 0.8, 1.7); p _trend = 0.29). However, the association was significantly positive among males (OR = 1.8 (95% CI: 1.1, 2.9); p _trend = 0.06). Total alcohol, beer, wine, or liquor intake was not associated with any major histopathologic subtype of NHL examined, apart from an association between high wine consumption and increased risk of chronic lymphocytic leukemia. Conclusions: Alcohol does not appear to be a major etiologic factor for overall NHL, nor its common subtypes.     

Urinary phytoestrogens and risk of prostate cancer in Jamaican men

We evaluated the relationship of spot urinary concentrations of phytoestrogens with total prostate cancer and tumor grade in a hospital-based case–control study in Jamaica. Urine samples were analyzed for genistein, daidzein, equol (isoflavones), and enterolactone (lignan) among newly diagnosed cases (n = 175) and controls (n = 194). Urinary concentrations of enterolactone (lignan) were higher among cases. There were no significant differences in median concentrations of isoflavone excretion. Compared with non-producers of equol (reference tertile), men who produced equol were at decreased risk of total prostate cancer (tertile 2: OR, 0.42; CI, 0.23–0.75) (tertile 3: OR, 0.48; CI, 0.26–0.87) (p _trend, 0.020) and high-grade disease (tertile 2: OR, 0.31; CI, 0.15–0.61) (tertile 3: OR, 0.29; CI, 0.13–0.60) (p _trend, 0.001). Higher concentrations of enterolactone were positively related to total prostate cancer (OR, 1.85; CI, 1.01–3.44; p _trend, 0.027) as well as high-grade disease (OR, 2.46; CI, 1.11–5.46; p _trend, 0.023). There were no associations between urinary excretion of genistein and daidzein with risk of prostate cancer. Producers of equol (isoflavone) may be at reduced risk of total- and high-grade prostate cancer whereas enterolactone may increase the likelihood of disease.     

Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women

Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre‐diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case‐control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76–9.72), p_trend = 0.0008 for estradiol, 3.67 (1.71–7.88), p_trend = 0.0007 for estrone, 2.15 (1.05–4.40), p_trend = 0.04 for androstenedione, 1.74 (0.88–3.46), p_trend = 0.06 for testosterone, 2.90 (1.42–5.90), p_trend = 0.002 for DHEAS and 0.46 (0.20–1.05), p_trend = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis. © 2003 Wiley‐Liss, Inc.     

Endogenous sex hormones and colorectal cancer survival among men and women

Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone-binding globulin (SHBG) with CRC-specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S. cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. We identified 174 deaths (83 CRC-specific deaths) in men and 106 deaths (70 CRC-specific deaths) in women. In men, higher circulating level of free testosterone was associated with lower risk of overall (the highest vs. lowest tertiles, HR = 0.66, 95% CI, 0.45–0.99, p_trend = 0.04) and possibly CRC-specific mortality (HR = 0.73, 95% CI, 0.41–1.29, p_trend = 0.27). We generally observed nonsignificant inverse associations for other sex steroids, and a positive association for SHBG with CRC-specific mortality among male patients. In women, however, we found a suggestive positive association of estrone with overall (HR = 1.54, 95% CI, 0.92–2.60, p_trend = 0.11) and CRC-specific mortality (HR = 1.96, 95% CI, 1.01–3.84, p_trend = 0.06). Total estradiol, free estradiol and free testosterone were generally suggestively associated with higher risk of mortality among female patients, although not statistically significant. These findings implicated a potential role of endogenous sex hormones in CRC prognosis, which warrant further investigation.     

Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer

Insulin‐like growth factor (IGF)?1 is associated with a higher risk of prostate cancer. IGF‐binding protein (IGFBP)?1, a marker for insulin activity, also binds IGF‐1 and inhibits its action. Data on IGFBP‐1 and prostate cancer risk are sparse and whether the IGF and insulin axes interact to affect prostate cancer carcinogenesis is unknown. We evaluated the independent and joint influence of prediagnostic plasma levels of IGFBP‐1 (fasting) and IGF‐1 on risk of prostate cancer among 957 cases and 1,021 controls with fasting levels of IGFBP‐1 and 1,709 cases and 1,778 controls with IGF‐1 nested within the Health Professionals Follow‐up Study. Unconditional logistic regression adjusting for matching factors was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Higher prediagnostic fasting IGFBP‐1 levels were associated with lower risk of prostate cancer (highest vs. lowest quartile OR = 0.67, 95% CI 0.52–0.86, p_trend = 0.003), which remained similar after adjusting for IGF‐1. Prediagnostic IGF‐1 was associated with increased risk of prostate cancer (highest vs. lowest quartile OR = 1.28, 95% CI = 1.05–1.56, p_trend = 0.01). The associations with each marker were primarily driven by lower‐grade and non‐advanced prostate cancer. Being low in IGFBP‐1 and high in IGF‐1 did not confer appreciable additional risk (p_interaction = 0.42). In summary, prediagnostic fasting IGFBP‐1 may influence prostate cancer carcinogenesis. Being low in IGFBP‐1 or high in IGF‐1 is sufficient to elevate the risk of prostate cancer.     

Dietary trace element intake and liver cancer risk: Results from two population‐based cohorts in China

Dietary factors have been hypothesized to affect the risk of liver cancer via various mechanisms, but the influence has been not well studied and the evidence is conflicting. We investigated associations of dietary trace element intake, assessed through a validated food frequency questionnaire, with risk of liver cancer in two prospective cohort studies of 132,765 women (1997–2013) and men (2002–2013) in Shanghai, China. The associations were first evaluated in cohort studies and further assessed in a case–control study nested within these cohorts adjusting for hepatitis B virus infection. For cohort analyses, Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. For nested case–control analyses, conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After a median follow‐up time of 15.2 years for the Shanghai Women's Health Study and 9.3 years for the Shanghai Men's Health Study, 192 women and 344 men developed liver cancer. Dietary intake of manganese was inversely associated with liver cancer risk (highest vs. lowest quintile, HR = 0.51, 95% CI: 0.35–0.73; p_trend = 0.001). Further adjustment for hepatitis B virus infection in the nested case–control study yielded a similar result (highest vs. lowest quintile, OR = 0.38, 95% CI: 0.21–0.69; p_trend < 0.001). No significant association was found between dietary intake of selenium, iron, zinc, copper and liver cancer risk. The results suggest that higher intake of manganese may be associated with a lower risk of liver cancer in China.     

Soluble levels of CD27 and CD30 are associated with risk of non‐Hodgkin lymphoma in three Chinese prospective cohorts

Prospective studies conducted in Western populations have suggested that alterations in soluble CD27 (sCD27) and soluble CD30 (sCD30), two markers indicative of B‐cell activation, are associated with risk of non‐Hodgkin lymphoma (NHL). Given that the characteristics of NHL in East Asia differ from the West and mechanistic commonalities between these populations with respect to the role of intermediate endpoint biomarkers in lymphomagenesis have not been explored, we conducted a pooled nested case‐control study from three prospective studies of Chinese men and women including 218 NHL cases and 218 individually matched controls. Compared with the lowest quartile, ORs (95% CIs) for the second, third and fourth quartiles of sCD27 were 1.60 (0.83–3.09), 1.94 (0.98–3.83) and 4.45 (2.25–8.81), respectively (p_trend = 0.000005). The corresponding ORs for sCD30 were 1.74 (0.85–3.58), 1.86 (0.94–3.67) and 5.15 (2.62–10.12; p_trend = 0.0000002). These associations remained statistically significant in individuals diagnosed with NHL 10 or more years after blood draw. Notably, the magnitude of the associations with NHL risk was very similar to those in Western populations in previous studies. These findings of the similar association between sCD27 or sCD30 and NHL risk across different populations support an important underlying mechanism of B‐cell activation in lymphomagenesis.     

Circulating sCD27 and sCD30 in pre-diagnostic samples collected fifteen years apart and future non-Hodgkin lymphoma risk

Elevated serum sCD27 and sCD30 from a single banked sample have been associated with future non-Hodgkin lymphoma risk (NHL); however, the etiologic relevance of this finding is unclear. To address this question, we conducted a case–control study (235 cases, 235 controls) nested within the CLUE-I and CLUE-II cohorts, which enrolled participants in 1974 and 1989 respectively in Washington County, Maryland. Our study features a subset of 102 cases and 102 controls with two banked pre-diagnostic samples each, collected 15 years apart. In analyses involving an individual sample per subject, both sCD27 and sCD30 were associated with NHL diagnosed up to 20 years later. In analyses involving repeated samples, cases were significantly more likely than controls to have higher analyte levels in the CLUE-II vs. CLUE-I sample for sCD27 (p = 0.006) but not sCD30 (p = 0.16). In joint analyses of dichotomized analyte levels in both samples, the strongest NHL association observed for sCD27 was for having below-median levels in CLUE-I and above-median levels in CLUE-II [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.4–9.2 vs. below-median levels in both). In joint analyses for sCD30, the strongest NHL association was observed for having above-median levels in both samples (OR 1.7, 95% CI 0.8–3.7), particularly for cases diagnosed >10 years after the CLUE-II sample (OR 2.4, 95% CI 0.9–6.7). Our findings suggest that sCD27 is a disease marker for NHL and add to the weight of evidence that elevated circulating sCD30 is a marker of increased NHL susceptibility.     

Progestin‐only and combined oral contraceptives and receptor‐defined premenopausal breast cancer risk: The Norwegian Women and Cancer Study

Receptor‐defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin‐only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of our study was to assess the effect of POC and COC use on hormone receptor‐defined breast cancer risk in premenopausal women in a prospective population‐based cohort – The Norwegian Women and Cancer Study (NOWAC). Information on OC use was collected from 74,862 premenopausal women at baseline. Updated information was applied when follow‐up information became available. Multiple imputation was performed to handle missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for breast cancer. 1,245 incident invasive breast cancer cases occurred. POC use ≥5 years was associated with ER+ (HR = 1.59, 95% CI 1.09– 2.32, p_trend = 0.03) and ER+/PR+ cancer (HR = 1.63, 95% CI 1.07–2.48, p_trend = 0.05), and was not associated with ER? (p_{heterogeneity} = 0.36) or ER?/PR? (p_{heterogeneity} = 0.49) cancer. COC use was associated with ER? and ER?/PR? cancer, but did not increase risk of ER+ and ER+/PR+ cancer. Current COC use gave different estimates for ER/PR‐defined subtypes (p_{heterogeneity} = 0.04). This is the first study to show significant associations between POC use and hormone receptor‐positive breast cancer. The lack of power to distinguish effects of POC use on subtype development calls for the need of larger studies to confirm our finding.     

Prediagnostic body size and breast cancer survival in the E3N cohort study

Obesity has been associated with poor breast cancer prognosis, however most studies have focused on body mass index (BMI) and few have considered the distribution of adipose tissue. We investigated associations between prediagnostic adiposity and breast cancer survival, considering BMI, waist and hip circumferences (WC and HC), and waist‐to‐hip ratio (WHR). Analyses included 3,006 women from the French E3N prospective cohort study diagnosed with primary invasive breast cancer between 1995 and 2008. We investigated overall, breast cancer‐specific, and disease‐free survival, overall and according to stage, menopausal and hormonal status and year of diagnosis, using Cox proportional hazard models adjusted for tumor characteristics and lifestyle risk factors. Women with a prediagnostic HC > 100 cm were at increased risk of death from all causes (hazard ratio (HR)_{>100vs < 95 cm} = 1.38, 95% Confidence Interval (CI) = 1.02–1.86, P_trend = 0.02) and from breast cancer (HR_{>100vs < 95 cm} = 1.50, CI = 1.03–2.17, P_trend = 0.03), and of second invasive cancer event (HR_{>100vs < 95 cm} = 1.36, CI = 1.11–1.67, P_trend = 0.002), compared to those with HC <95 cm. Associations were stronger after adjustment for BMI. BMI, WC and WHR were not associated with survival after breast cancer. Our study underlines the importance of going beyond BMI when studying the association between adiposity and breast cancer survival. Further studies should be conducted to confirm our results on hip circumference.     

Inverse associations of dietary fiber and menopausal hormone therapy with colorectal cancer risk in the Multiethnic Cohort Study

In the Multiethnic Cohort Study, we previously reported that dietary fiber intake was inversely associated with colorectal cancer risk in men only. In women, the inverse relationship was weaker and appeared to be confounded by menopausal hormone therapy (MHT). We re‐examined this observation with a greatly increased power. Using Cox proportional hazards models, we analyzed data from 187,674 participants with 4,692 cases identified during a mean follow‐up period of 16 years. In multivariable‐adjusted models, dietary fiber intake was inversely associated with colorectal cancer risk in both sexes: HR = 0.73, 95% CI: 0.61–0.89 for highest vs. lowest quintile, p_trend = 0.0020 in men and HR = 0.76, 95% CI: 0.62–0.91, p_trend = 0.0067 in women. Postmenopausal women who ever used MHT had a 19% lower risk of colorectal cancer (95% CI: 0.74–0.89) compared with MHT never users. In a joint analysis of dietary fiber and MHT, dietary fiber intake was associated with a lower colorectal cancer risk in MHT never users (HR = 0.75, 95% CI: 0.59–0.95, p_trend = 0.045), but did not appear to further decrease the colorectal cancer risk of MHT ever users (p_trend = 0.11). Our results support the overall protective roles of dietary fiber and MHT against colorectal cancer and suggest that dietary fiber may not lower risk further among women who ever used MHT. If confirmed, these results would suggest that MHT and dietary fiber may share overlapping mechanisms in protecting against colorectal cancer.     

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (p_homogeneity = 0.42). This risk increased linearly with duration of use (p_trend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (p_homogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.     

Intake of trans fatty acids from partially hydrogenated vegetable and fish oils and ruminant fat in relation to cancer risk

Intake of trans fatty acids (TFA) may influence systemic inflammation, insulin resistance and adiposity, but whether TFA intake influences cancer risk is insufficiently studied. We examined the association between TFA intake from partially hydrogenated vegetable oils (PHVO‐TFA), partially hydrogenated fish oils (PHFO‐TFA), and ruminant fat (rTFA) and cancer risk in the Norwegian counties study, a large cohort study with a participation rate >80%. TFA intake was assessed three times in 1974–1988 by questionnaire. A total of 77,568 men and women were followed up through 2007, during which time 12,004 cancer cases occurred. Hazard ratios (HRs) and confidence intervals (CIs) were estimated with Cox regression for cancer sites with ≥150 cases during follow‐up. Significantly increased or decreased risks were found when comparing the highest and lowest intake categories (HRs, 95% CIs) for PHVO‐TFA and pancreatic cancer in men (0.52, 0.31–0.87) and non‐Hodgkin lymphoma (NHL) in both genders (0.70, 0.50–0.98); PHFO‐TFA and rectal cancer (1.43, 1.09–1.88), prostate cancer (0.82, 0.69–0.96), and multiple myeloma (2.02, 1.24–3.28); and rTFA and all cancers (1.09, 1.02–1.16), cancer of the mouth/pharynx (1.59, 1.08–2.35), NHL (1.47, 1.06–2.04) and multiple myeloma (0.45, 0.24–0.84). Furthermore, positive trends were found for PHFO‐TFA and stomach cancer (p_trend = 0.01) and rTFA and postmenopausal breast cancer (p_trend = 0.03). Inverse trends were found for PHVO‐TFA and all cancers (p_trend = 0.006) and cancer of the central nervous system in women (p_trend = 0.005). PHFO‐TFA, but not PHVO‐TFA, seemed to increase cancer risk. The increased risks observed for rTFA may be linked to saturated fat.     

Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled Project

Multiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case‐control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime‐days (LD) (days/year handled × years of use). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, province/state of residence, use of proxy respondents and selected medical conditions. Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28–3.21), captan (OR = 1.98, 95% CI = 1.04–3.77) and DDT (OR = 1.44, 95% CI = 1.05–1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40–7.23) for ≤10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05–5.64; p_trend = 0.01). For captan, ≤17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32–9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81–6.43; p_trend = 0.01). An increasing trend (p_trend = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95–3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT.