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- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 2. |
- Jayasekara, Harindra, et al.
(författare)
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Alcohol consumption for different periods in life, intake pattern over time and all-cause mortality
- 2015
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Ingår i: Journal of Public Health. - : Oxford University Press (OUP). - 1741-3842 .- 1741-3850. ; 37:4, s. 625-633
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conventionally, cohort studies have assessed the association between alcohol and all-cause mortality by using alcohol intake at enrolment.Methods: In theMelbourne Collaborative Cohort Study, participants were asked about usual frequency and quantity of beverage-specific alcoholintake for 10-year periods starting at age 20 from which current, past and lifetime intakes were calculated.We used Cox regression to estimate hazardratios for mortality for 39 577 participants of theMelbourne Collaborative Cohort Study aged 40–69 at baseline.Results: After a mean follow-up of 15 years/person, we identified 4639 deaths. Associations between all-cause mortality and lifetime, current(baseline) and past intakewere J shaped, with lower mortality at low intake (e.g. ,40 g/day for men and 10 g/day for women using lifetime intake)and elevated mortality at higher intake. Formen, consistent light-to-moderate drinking (.0–39/.0–39 g/day) from age 20 to baseline agewasassociated with a 16% lower mortality, while heavy drinking at both ages (80/40 and 40/0 g/day) was associated with higher mortality comparedwith stable abstinence.Conclusions: Our findings support a reduced mortality risk associated with low-dose drinking but also highlight a higher mortality risk for consistentheavy drinking from a young age.
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| 3. |
- Jayasekara, Harindra, et al.
(författare)
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Lifetime alcohol consumption and upper aero-digestive tract cancer risk in the Melbourne Collaborative Cohort Study
- 2015
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 26:2, s. 297-301
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Tidskriftsartikel (refereegranskat)abstract
- Cohort studies have rarely examined the association between upper aero-digestive tract (UADT) cancer risk and lifetime alcohol intake. We examined the associations between incident squamous cell carcinoma of the UADT (oral cavity, pharynx, larynx, and esophagus) and alcohol intake for different periods in life using data from the Melbourne Collaborative Cohort Study. Usual alcohol intake for 10-year periods from age 20 was calculated using recalled frequency and quantity of beverage-specific consumption. Cox regression with age as the time axis was performed to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the associations of UADT cancer with alcohol intake for different periods in life compared with abstention. During a mean follow-up of 16.2 person-years, 98 incident cases of UADT cancer were identified. We observed a dose-dependent association between lifetime alcohol intake and the risk of UADT cancer (multivariable-adjusted HR 2.67, 95 % CI 1.27-5.60 for an intake of a parts per thousand yen40 g/day and multivariable-adjusted HR 1.16, 95 % CI 1.06-1.28 for a 10 g/day increment in intake). A positive association with baseline alcohol intake (multivariable-adjusted HR 1.12, 95 % CI 1.02-1.24 for a 10 g/day increment in intake) was found to be a slightly weaker predictor of risk than lifetime intake. Limiting alcohol intake from early adulthood may reduce UADT cancer risk.
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