Dataset Information

Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study.

ABSTRACT: BACKGROUND:Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS:We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS:After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION:Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING:Cancer Research UK and the UK Medical Research Council.

SUBMITTER: Travis RC

PROVIDER: S-EPMC2890858 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study.

Travis Ruth C RC Reeves Gillian K GK Green Jane J Bull Diana D Tipper Sarah J SJ Baker Krys K Beral Valerie V Peto Richard R Bell John J Zelenika Diana D Lathrop Mark M

Lancet (London, England) 20100603 9732

<h4>Background</h4>Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study.<h4>Methods</h4>We tested gene-environment interactions in 7610 women wh ...[more]

PMID: 20605201

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Project description:BackgroundPoor health can cause unhappiness and poor health increases mortality. Previous reports of reduced mortality associated with happiness could be due to the increased mortality of people who are unhappy because of their poor health. Also, unhappiness might be associated with lifestyle factors that can affect mortality. We aimed to establish whether, after allowing for the poor health and lifestyle of people who are unhappy, any robust evidence remains that happiness or related subjective measures of wellbeing directly reduce mortality.MethodsThe Million Women Study is a prospective study of UK women recruited between 1996 and 2001 and followed electronically for cause-specific mortality. 3 years after recruitment, the baseline questionnaire for the present report asked women to self-rate their health, happiness, stress, feelings of control, and whether they felt relaxed. The main analyses were of mortality before Jan 1, 2012, from all causes, from ischaemic heart disease, and from cancer in women who did not have heart disease, stroke, chronic obstructive lung disease, or cancer at the time they answered this baseline questionnaire. We used Cox regression, adjusted for baseline self-rated health and lifestyle factors, to calculate mortality rate ratios (RRs) comparing mortality in women who reported being unhappy (ie, happy sometimes, rarely, or never) with those who reported being happy most of the time.FindingsOf 719,671 women in the main analyses (median age 59 years [IQR 55-63]), 39% (282,619) reported being happy most of the time, 44% (315,874) usually happy, and 17% (121,178) unhappy. During 10 years (SD 2) follow-up, 4% (31,531) of participants died. Self-rated poor health at baseline was strongly associated with unhappiness. But after adjustment for self-rated health, treatment for hypertension, diabetes, asthma, arthritis, depression, or anxiety, and several sociodemographic and lifestyle factors (including smoking, deprivation, and body-mass index), unhappiness was not associated with mortality from all causes (adjusted RR for unhappy vs happy most of the time 0·98, 95% CI 0·94-1·01), from ischaemic heart disease (0·97, 0·87-1·10), or from cancer (0·98, 0·93-1·02). Findings were similarly null for related measures such as stress or lack of control.InterpretationIn middle-aged women, poor health can cause unhappiness. After allowing for this association and adjusting for potential confounders, happiness and related measures of wellbeing do not appear to have any direct effect on mortality.FundingUK Medical Research Council, Cancer Research UK.

Project description:BackgroundEpidemiological studies have shown that taller people are at increased risk of cancer, but it is unclear if height-associated risks vary by cancer site, or by other factors such as smoking and socioeconomic status. Our aim was to investigate these associations in a large UK prospective cohort with sufficient information on incident cancer to allow direct comparison of height-associated risk across cancer sites and in relation to major potential confounding and modifying factors.MethodsInformation on height and other factors relevant for cancer was obtained in 1996-2001 for middle-aged women without previous cancer who were followed up for cancer incidence. We used Cox regression models to calculate adjusted relative risks (RRs) per 10 cm increase in measured height for total incident cancer and for 17 specific cancer sites, taking attained age as the underlying time variable. We also did a meta-analysis of published results from prospective studies of total cancer risk in relation to height.Findings1 297 124 women included in our analysis were followed up for a total of 11·7 million person-years (median 9·4 years per woman, IQR 8·4-10·2), during which time 97 376 incident cancers occurred. The RR for total cancer was of 1·16 (95% CI 1·14-1·17; p<0·0001) for every 10 cm increase in height. Risk increased for 15 of the 17 cancer sites we assessed, and was statistically significant for ten sites: colon (RR per 10 cm increase in height 1·25, 95% CI 1·19-1·30), rectum (1·14, 1·07-1·22), malignant melanoma (1·32, 1·24-1·40), breast (1·17, 1·15-1·19), endometrium (1·19, 1·13-1·24), ovary (1·17, 1·11-1·23), kidney (1·29, 1·19-1·41), CNS (1·20, 1·12-1·29), non-Hodgkin lymphoma (1·21, 1·14-1·29), and leukaemia (1·26, 1·15-1·38). The increase in total cancer RR per 10 cm increase in height did not vary significantly by socioeconomic status or by ten other personal characteristics we assessed, but was significantly lower in current than in never smokers (p<0·0001). In current smokers, smoking-related cancers were not as strongly related to height as were other cancers (RR per 10 cm increase in height 1·05, 95% CI 1·01-1·09, and 1·17, 1·13-1·22, respectively; p=0·0004). In a meta-analysis of our study and ten other prospective studies, height-associated RRs for total cancer showed little variation across Europe, North America, Australasia, and Asia.InterpretationCancer incidence increases with increasing adult height for most cancer sites. The relation between height and total cancer RR is similar in different populations.FundingCancer Research UK and the UK Medical Research Council.

Dataset Information

Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study.

Publications

Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study.

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