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Background: Second-hand smoke (SHS) is not an established risk factor for breast cancer. We examined exposure to SHS from parents during childhood and breast-cancer risk overall and by oestrogen- and progesterone-receptor status in the Norwegian Women and Cancer Study. Furthermore, we utilized our nationally representative prospective cohort study to estimate the fraction of breast cancer attributable to parental SHS during childhood.Methods: We followed 45 923 never-smoking women, aged 34-70 years, who completed a baseline questionnaire between 1991 and 2007 through linkages to national registries through December 2018. We used Cox proportional-hazards models to estimate age-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). We estimated the attributable and the population attributable fraction of breast cancer with 95% CIs.Results: During a mean follow-up of 19.8 (6.8) years, 2185 women developed invasive breast cancer, confirmed by histology. Women exposed to SHS from parents during childhood had an 11% higher (95% CI: 1.02-1.22) risk of breast cancer compared with those who were not. No difference was found for oestrogen (Pheterogeneity = 0.31) and progesterone (Pheterogeneity = 0.95) receptor status. For women exposed, the attributable fraction was 10.3% (95% CI: 1.8-18.0), whereas the population attributable fraction of breast cancer was 7.0% (95% CI: 1.0-13.0).Conclusions: Our results suggest that 1 in 14 breast-cancer cases could have been avoided in the absence of SHS exposure from parents during childhood in a population of never-smoking women. The cancer burden attributable to SHS may be underestimated. [ABSTRACT FROM AUTHOR]

Lower prediagnostic circulating 25‐hydroxyvitamin D (25[OH]D)—considered the best marker of total vitamin D exposure—is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D‐binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D‐mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study‐II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 ‐ <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable‐adjusted hazard ratios (HRs) for CRC‐specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44‐3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68‐1.22) among cases without Gc2 (Pinteraction =.0002). The corresponding HRs for all‐cause mortality were 1.80 (95% CI 1.24‐2.60) among those with Gc2, and 1.12 (95% CI 0.84‐1.51) among those without Gc2 (Pinteraction =.004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis. What's new? Vitamin D regulates molecular pathways that are relevant to cancer progression. In patients with colorectal cancer (CRC), low serum levels of vitamin D have been associated with increased mortality. A protein called GC binds vitamin D and delivers it to tissues. In this study, the authors found that the increased mortality risk with low vitamin D was only seen in those CRC patients who carry a genetic variant of GC called Gc2. These results may help to identify a vulnerable subgroup of CRC patients, who may particularly benefit from vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Early‐adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual‐level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18–24 years and other breast cancer risk factors showed that weight gain from ages 18–24 to 35–44 or to 45–54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.95–0.98) and with oestrogen‐receptor(ER)‐positive breast cancer (HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.94–0.98). Weight gain from ages 25–34 was inversely associated with ER‐positive breast cancer only and weight gain from ages 35–44 was not associated with risk. None of these weight gains were associated with ER‐negative breast cancer. Weight loss was not consistently associated with overall or ER‐specific risk after adjusting for initial weight. Weight increase from early‐adulthood to ages 45–54 years is associated with a reduced premenopausal breast cancer risk independently of early‐adulthood weight. Biological explanations are needed to account for these two separate factors. What's new? Body weight in childhood and early adulthood plays a key role in determining premenopausal breast cancer risk but little is conclusively known about how subsequent weight changes affect this risk. Here the authors pooled results from existing studies on weight changes and breast cancer risk including more than 600,000 premenopausal women. The results show that weight gain >10–15 kg from early adulthood on lowers the risk of developing premenopausal breast cancer, providing further evidence of body weight as an important determinant of breast cancer risk. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45–75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993–1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine if the smoking-related higher breast cancer risk was similar for the five race/ethnicity groups in the Multiethnic Cohort (MEC) study and by oestrogen (ER) and progesterone (PR) receptor status.Methods: From 1993 to 2013, we followed 67 313 women who were enrolled in the MEC study at 45-75 years of age. We identified breast cancer cases and tumour receptor status via linkage to the Hawaii and California Surveillance, Epidemiology and End Results Program cancer registries through December 2013. We used Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios with 95% confidence intervals (CI).Results: During a mean follow-up of 16.7 years, we identified 4230 incident, invasive breast cancer cases. Compared with parous never smokers, parous ever smokers who had smoked more than 5 years before their first live childbirth had a higher risk of breast cancer overall of 31% (95% CI: 1.14-1.51). This higher risk was 51% (95% CI: 1.05-2.16) for African Americans, 66% (95% CI: 1.10-2.50) for Native Hawaiians, 42% (95% CI: 1.13-1.78) for Whites, 37% (95% CI: 1.17-1.61) for ER-positive (ER+) tumours and 33% (95% CI: 1.11-1.59) for PR+ tumours. No difference was suggested by racial/ethnic groups (Pheterogeneity = 0.15) or tumour receptor status (Pheterogeneity = 0.60 by ER status and 0.95 by PR status).Conclusions: We find that the higher breast cancer risk related to smoking is similar across racial/ethnic groups and by ER and PR status, indicating that breast cancer should be considered as a smoking-related cancer. [ABSTRACT FROM AUTHOR]

Background: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and Findings: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4–0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Conclusions: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors. [ABSTRACT FROM AUTHOR]

We prospectively examined the association between smoking and the risk of breast cancer in a racially/ethnically diverse population comprising mainly women who did not drink alcohol. From 1993 to 2010, we followed 83,300 women who were enrolled in the Multiethnic Cohort Study at 45-75 years of age. We identified cancer cases via linkage to the Surveillance, Epidemiology, and End Results Program cancer registries that covered the states of Hawaii and California through December 2010. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals while adjusting for confounders that were decided a priori. During a mean follow-up of 15 years, 4,484 women developed invasive breast cancer. Compared with parous never smokers, women who had smoked for more than 20 pack-years and initiated smoking more than 5 years before their first childbirth had an overall risk of breast cancer that was 35% higher (hazard ratio = 1.35, 95% confidence interval: 1.13, 1.63). Among women who did not drink alcohol, the risk was 40% higher (hazard ratio = 1.40, 95% confidence interval: 1.08,1.81). This higher riskdid not significantly differ among racial/ethnic groups (Pinteraction = 0.82). We found that various measures of smoking exposure were associated with a higher risk of breast cancer, especially smoking initiated many years before first childbirth, and that risk did not differ by alcohol consumption (yes vs. no) or racial/ethnic group. [ABSTRACT FROM AUTHOR]