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Genetic Factors, Adherence to Healthy Lifestyle Behavior, and Risk of Invasive Breast Cancer Among Women in the UK Biobank.

ABSTRACT: BACKGROUND:Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal. METHODS:Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146?326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci. RESULTS:Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low = 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29%, and 32% reductions in risk of invasive breast cancer in the low, intermediate, and high PRS groups, respectively (HRhigh vs low = 0.70, 95% CI = 0.56 to 0.88; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women. CONCLUSION:Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.

SUBMITTER: Arthur RS

PROVIDER: S-EPMC7492765 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Genetic Factors, Adherence to Healthy Lifestyle Behavior, and Risk of Invasive Breast Cancer Among Women in the UK Biobank.

Arthur Rhonda S RS Wang Tao T Xue Xiaonan X Kamensky Victor V Rohan Thomas E TE

Journal of the National Cancer Institute 20200901 9

<h4>Background</h4>Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal.<h4>Methods</h4>Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146 326 women from the U ...[more]

PMID: 31899501

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Project description:BackgroundContested evidence suggests that obesity confers no risk to health in people who have a healthy lifestyle, particularly if there are no metabolic complications of obesity. The aim was to examine the association between adherence to lifestyle recommendations and the absence of metabolic complications on the incident or fatal cardiovascular disease and all-cause mortality across different categories of body mass index (BMI).MethodsThis contemporary prospective cohort study included 339,902 adults without cardiovascular disease at baseline, recruited between 2006 and 2010 from the UK Biobank and followed until 2018-2020. The main exposures were four healthy lifestyle behaviours: never smoker, alcohol intake ≤ 112g/ week, 150 min moderate physical activity or 75 min vigorous activity/week, ≥ 5 servings of fruit or vegetables/day, and we assessed these overall and across the BMI groups. Metabolic complications of excess adiposity were hypertension, diabetes and hyperlipidaemia, and we examined whether obesity was associated with increased risk in the absence of these complications. The outcomes were all-cause mortality, death from, and incident cardiovascular disease (CVD).ResultsIndividuals who met four lifestyle recommendations but had excess weight had higher all-cause mortality; for BMI 30-34.9 kg/m2, the hazard ratio (HR) was 1.42 (95% confidence interval 1.20 to 1.68), and for BMI ≥ 35 kg/m2, HR was 2.17 (95% CI 1.71 to 2.76). The risk was lower, but still increased for people with no metabolic complications; for all-cause mortality, BMI 30-34.9 kg/m2 had an HR of 1.09 (95% CI 0.99 to 1.21), and BMI ≥ 35 kg/m2 had an HR of 1.44 (95% CI 1.19 to 1.74) for all-cause mortality. Similar patterns were found for incident and fatal CVD.ConclusionsMeeting healthy lifestyle recommendations, or the absence of metabolic complications of obesity offsets some, but not all, of the risk of subsequent CVD, and premature mortality in people with overweight or obesity. Offering support to achieve and maintain a healthy weight and to adopt healthy behaviours are likely to be important components in effective preventative healthcare.

Project description:BackgroundCardiometabolic disease (CMD) increases the risk of mortality, but the extent to which this can be offset by adherence to a healthy lifestyle is unknown. We aimed to investigate whether and to what extent a combination of healthy lifestyle is associated with lower risk of total mortality that related to CMD.MethodsData for this prospective analysis was sourced from the UK Biobank with 356,967 participants aged 37 to 73 years between 2006 and 2010. Adherence to a healthy lifestyle was determined on the basis of four factors: no smoking, healthy diet, body mass index < 30 kg/m2, and regular physical activity. CMD was defined as any of incidence of diabetes, coronary heart disease and stroke at baseline. Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) of the associations of CMDs and lifestyle factors with total mortality.ResultsDuring a median follow-up of 13 years, a total of 21,473 death events occurred. The multivariable-adjusted HRs of mortality were 1.49 (95% CI 1.53-1.56) for one, 2.17 (95% CI 2.01-2.34) for two, and 3.75 (95% CI 3.04-4.61) for three CMDs. In joint exposure analysis, compared with CMDs-free and a favorable lifestyle, the HRs of mortality were 2.57 (95% CI 2.38-2.78) for patients with CMDs plus an unfavorable lifestyle and 1.58 (95% CI 1.50-1.66) for those with CMDs plus a favorable lifestyle. A favorable lifestyle attenuates the CMDs-related risk of mortality by approximately 63%. The mortality risk of CMDs-free people but have unfavorable lifestyle was higher than those who have over one CMDs but have favorable lifestyle.ConclusionThe potential effect of an increasing number of CMDs on total mortality appears additive, adherence to a healthy lifestyle may attenuate the CMDs-related mortality risk by more than 60%. These findings highlight the potential importance of lifestyle interventions to reduce risk of mortality across entire populations, even in patients with CMDs.

Project description:To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [β (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors. Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

Project description:ImportanceGenetic and lifestyle factors are related to thyroid cancer (TC). Whether a healthy lifestyle is associated with TC and could attenuate the influence of genetic variants in TC remains equivocal.ObjectivesTo examine the associations between genetics and healthy lifestyle with incident TC and whether adherence to a healthy lifestyle modifies the association between genetic variants and TC.Design, setting, and participantsA prospective cohort study using UK Biobank data recruited 502 505 participants aged 40 to 69 years between March 13, 2006, and October 1, 2010. A total of 307 803 participants of European descent were recruited at baseline, and 264 956 participants were available for the present study. Data analysis was conducted from November 1, 2021, to April 22, 2022.ExposuresLifestyle behaviors were determined by diet index, physical activity, weight, smoking, and alcohol consumption. Lifestyle was categorized as unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5). The polygenic risk score (PRS) was derived from a meta-genome-wide association study using 3 cohorts and categorized as low, intermediate, and high.Main outcomes and measuresThyroid cancer was defined using the International Classification of Diseases, Ninth Revision (code 193), International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (code C73), and self-report (code 1065).ResultsOf 264 956 participants, 137 665 were women (52%). The median age was 57 (IQR, 49-62) years. During a median follow-up of 11.1 (IQR, 10.33-11.75) years (2 885 046 person-years), 423 incident TCs were ascertained (14.66 per 100 000 person-years). Higher PRSs were associated with TC (hazard ratio [HR], 2.25; 95% CI, 1.91-2.64; P = 8.65 × 10-23). An unfavorable lifestyle was also associated with a higher risk of TC (HR, 1.93; 95% CI, 1.50-2.49; P < .001). When stratified by PRS, unfavorable lifestyle was associated with TC in the higher PRS group (favorable vs unfavorable HR, 0.52; 95% CI, 0.37-0.73; P < .001). Furthermore, participants with both a high PRS and unfavorable lifestyle had the highest risk of TC (HR, 4.89; 95% CI, 3.03-7.91; P < .001).Conclusions and relevanceIn this prospective cohort study, genetic and lifestyle factors were independently associated with incident TC, which suggests that a healthier lifestyle may attenuate the deleterious influence of genetics on the risk of TC in individuals of European descent.

Project description:BackgroundWhether a healthy lifestyle impacts longevity in the presence of multimorbidity is unclear. We investigated the associations between healthy lifestyle and life expectancy in people with and without multimorbidity.Methods and findingsA total of 480,940 middle-aged adults (median age of 58 years [range 38-73], 46% male, 95% white) were analysed in the UK Biobank; this longitudinal study collected data between 2006 and 2010, and participants were followed up until 2016. We extracted 36 chronic conditions and defined multimorbidity as 2 or more conditions. Four lifestyle factors, based on national guidelines, were used: leisure-time physical activity, smoking, diet, and alcohol consumption. A combined weighted score was developed and grouped participants into 4 categories: very unhealthy, unhealthy, healthy, and very healthy. Survival models were applied to predict life expectancy, adjusting for ethnicity, working status, deprivation, body mass index, and sedentary time. A total of 93,746 (19.5%) participants had multimorbidity. During a mean follow-up of 7 (range 2-9) years, 11,006 deaths occurred. At 45 years, in men with multimorbidity an unhealthy score was associated with a gain of 1.5 (95% confidence interval [CI] -0.3 to 3.3; P = 0.102) additional life years compared to very unhealthy score, though the association was not significant, whilst a healthy score was significantly associated with a gain of 4.5 (3.3 to 5.7; P < 0.001) life years and a very healthy score with 6.3 (5.0 to 7.7; P < 0.001) years. Corresponding estimates in women were 3.5 (95% CI 0.7 to 6.3; P = 0.016), 6.4 (4.8 to 7.9; P < 0.001), and 7.6 (6.0 to 9.2; P < 0.001) years. Results were consistent in those without multimorbidity and in several sensitivity analyses. For individual lifestyle factors, no current smoking was associated with the largest survival benefit. The main limitations were that we could not explore the consistency of our results using a more restrictive definition of multimorbidity including only cardiometabolic conditions, and participants were not representative of the UK as a whole.ConclusionsIn this analysis of data from the UK Biobank, we found that regardless of the presence of multimorbidity, engaging in a healthier lifestyle was associated with up to 6.3 years longer life for men and 7.6 years for women; however, not all lifestyle risk factors equally correlated with life expectancy, with smoking being significantly worse than others.

Project description:ImportanceThe association between noninherited factors, including lifestyle factors, and the risk of breast cancer (BC) in women and the association between BC and genetic makeup are only partly characterized. A study using data on current genetic stratification may help in the characterization.ObjectiveTo examine the association between healthier lifestyle habits and BC risk in genetically predisposed groups.Design, setting, and participantsData from UK Biobank, a prospective cohort comprising 2728 patients with BC and 88 489 women without BC, were analyzed. The data set used for the analysis was closed on March 31, 2019. The analysis was restricted to postmenopausal white women. Classification of healthy lifestyle was based on Cancer Research UK guidance (healthy weight, regular exercise, no use of hormone replacement therapy for more than 5 years, no oral contraceptive use, and alcohol intake <3 times/wk). Three groups were established: favorable (≥4 healthy factors), intermediate (2-3 healthy factors), and unfavorable (≤1 healthy factor). The genetic contribution was estimated using the polygenic risk scores of 305 preselected single-nucleotide variations. Polygenic risk scores were categorized into 3 tertiles (low, intermediate, and high).Main outcomes and measuresCox proportional hazards regression was used to assess the hazard ratios (HRs) of the lifestyles and polygenic risk scores associated with a malignant neoplasm of the breast.ResultsMean (SD) age of the 2728 women with BC was 60.1 (5.5) years, and mean age of the 88 489 women serving as controls was 59.4 (4.9) years. The median follow-up time for the cohort was 10 years (maximum 13 years) (interquartile range, 9.44-10.82 years). Women with BC had a higher body mass index (relative risk [RR], 1.14; 95% CI, 1.05-1.23), performed less exercise (RR, 1.12; 95% CI, 1.01-1.25), used hormonal replacement therapy for longer than 5 years (RR, 1.23; 95% CI, 1.13-1.34), used more oral contraceptives (RR, 1.02; 95% CI, 0.93-1.12), and had greater alcohol intake (RR, 1.11; 95% CI, 1.03-1.19) compared with the controls. Overall, 20 657 women (23.3%) followed a favorable lifestyle, 60 195 women (68.0%) followed an intermediate lifestyle, and 7637 women (8.6%) followed an unfavorable lifestyle. The RR of the highest genetic risk group was 2.55 (95% CI, 2.28-2.84), and the RR of the most unfavorable lifestyle category was 1.44 (95% CI, 1.25-1.65). The association of lifestyle and BC within genetic subgroups showed lower HRs among women following a favorable lifestyle compared with intermediate and unfavorable lifestyles among all of the genetic groups: women with an unfavorable lifestyle had a higher risk of BC in the low genetic group (HR, 1.63; 95% CI, 1.13-2.34), intermediate genetic group (HR, 1.94; 95% CI, 1.46-2.58), and high genetic group (HR, 1.39; 95% CI, 1.11-1.74) compared with the reference group of favorable lifestyle. Intermediate lifestyle was also associated with a higher risk of BC among the low genetic group (HR, 1.40; 95% CI, 1.09-1.80) and the intermediate genetic group (HR, 1.37; 95% CI, 1.12-1.68).Conclusions and relevanceIn this cohort study of data on women in the UK Biobank, a healthier lifestyle with more exercise, healthy weight, low alcohol intake, no oral contraceptive use, and no or limited hormonal replacement therapy use appeared to be associated with a reduced level of risk for BC, even if the women were at higher genetic risk for BC.

Dataset Information

Genetic Factors, Adherence to Healthy Lifestyle Behavior, and Risk of Invasive Breast Cancer Among Women in the UK Biobank.

Publications

Genetic Factors, Adherence to Healthy Lifestyle Behavior, and Risk of Invasive Breast Cancer Among Women in the UK Biobank.

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