Ethnic differences in breast cancer incidence in England are due to differences in known risk factors for the disease: prospective study.

BACKGROUND: In the United Kingdom, breast cancer incidence is lower in South Asian and Black women than in White women, but the extent to which this is due to known risk factors is unknown. In a large prospective study, we describe breast cancer incidence by ethnicity, before and after adjustment for known risk factors for the disease. METHODS: Women were recruited into the Million Women Study in 1996-2001, when information on reproductive and lifestyle factors known to influence the risk of breast cancer was obtained. Ethnicity was determined from study questionnaires and hospital admission data. Cox regression models were used to calculate adjusted relative risks (RR) for incident breast cancer in South Asians and Blacks compared with Whites. RESULTS: Analyses included 5877 South Asian, 4919 Black, and 1,038,144 White women in England. The prevalence of 8 out of the 9 risk factors for breast cancer examined, differed substantially by ethnicity (P<0.001 for each), such that South Asian and Black women were at a lower risk of the disease than White women. During 12.2 years of follow-up incident breast cancer occurred in 217 South Asians, 180 Blacks, and 45,191 Whites. As expected, breast cancer incidence was lower in South Asians (RR=0.82, 95% CI 0.72-0.94) and Blacks (RR=0.85, 0.73-0.98) than in Whites when the analyses were adjusted only for age and region of residence. However, after additional adjustment for the known risk factors for the disease, breast cancer incidence was similar to that of Whites, both in South Asians (0.95, 0.83-1.09) and in Blacks (0.91, 0.78-1.05). CONCLUSION: South Asian and Black women in England have lower incidence rates of breast cancer than White women, but this is largely, if not wholly, because of differences in known risk factors for the disease.

Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom.

BACKGROUND: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. METHODS: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. RESULTS: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99-1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82-2.27), or breast cancer (RR=1.09, 95% CI: 1.02-1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65-0.96). CONCLUSIONS: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.

Fluid intake and incidence of renal cell carcinoma in UK women.

BACKGROUND: It has been suggested that the apparent protective effect of alcohol intake on renal cell carcinoma may be due to the diluting effect of carcinogens by a high total fluid intake. We assessed the association between intakes of total fluids and of specific beverages on the risk of renal cell carcinoma in a large prospective cohort of UK women. METHODS: Information on beverage consumption was obtained from a questionnaire sent ∼3 years after recruitment into the Million Women Study. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for renal cell carcinoma associated with beverage consumption adjusted for age, region of residence, socioeconomic status, smoking, and body mass index. RESULTS: After an average of 5.2 years of follow-up, 588 cases of renal cell carcinoma were identified among 779,369 women. While alcohol intake was associated with a reduced risk of renal cell carcinoma (RR for ≥ 2 vs <1 drink per day: 0.76; 95% CI: 0.61-0.96; P for trend=0.02), there was no association with total fluid intake (RR for ≥ 12 vs <7 drinks per day: 1.15; 95% CI: 0.91-1.45; P for trend=0.3) or with intakes of specific beverages. CONCLUSIONS: The apparent protective effect of alcohol on the risk of renal cell carcinoma is unlikely to be related to a high fluid intake.

Reproductive history, hormonal factors and the incidence of hip and knee replacement for osteoarthritis in middle-aged women.

OBJECTIVES: To examine the effect of reproductive history and use of hormonal therapies on the risk of hip and knee joint replacement for osteoarthritis. METHODS: A prospective study of 1.3 million women aged on average 56 years at recruitment and followed-up through linkage to routinely collected hospital admission records was conducted. The adjusted relative risk (RR) of hip and knee replacement for osteoarthritis was examined in relation to parity, age at menarche, menopausal status, age at menopause and use of hormonal therapies. RESULTS: Over a mean of 6.1 person-years of follow-up, 12 124 women had a hip replacement and 9977 a knee replacement. The risk of joint replacement increased with increasing parity and the effect was greater for the knee than the hip: increase in RR of 2% (95% CI 1 to 4%) per birth for hip replacement and 8% (95% CI 6 to 10%) for knee replacement. An early age at menarche slightly increased the risk of hip and knee replacement (relative risk for menarche < or =11 years versus 12 years, 1.09 (95% CI 1.03 to 1.16) and 1.15 (95% CI 1.08 to 1.22), respectively). Menopausal status and age at menopause were not clearly associated with risk. Current use of postmenopausal hormone therapy was associated with a significant increase in the incidence of hip and knee replacement (RR 1.38 (95% CI 1.30 to 1.46) and RR 1.58 (95% CI 1.48 to 1.69), respectively) while previous use of oral contraceptives was not (RR 1.02 (95% CI 0.98 to 1.06) and RR 1.00 (95% CI 0.96 to 1.04) for hip and knee, respectively). CONCLUSIONS: Hormonal and reproductive factors affect the risk of hip and knee replacement, more so for the knee than the hip. The reasons for this are unclear.

Paternal preconceptional radiation exposure in the nuclear industry and leukaemia and non-Hodgkin's lymphoma in young people in Scotland.

OBJECTIVE: To determine if a relation exists between paternal exposure to relatively high levels of radiation in the Scottish nuclear industry and the risk of leukaemia and non-Hodgkin's lymphoma is subsequently conceived children. DESIGN: Matched case-control study with three controls for each case. SETTING: The whole of Scotland. SUBJECTS: The fathers of 1024 children with leukaemia and 237 children with non-Hodgkin's lymphoma diagnosed in Scotland below the age of 25 among those born in Scotland since nuclear operations began (in 1958) and the fathers of 3783 randomly chosen controls. The fathers of 80 children with leukaemia and 16 with non-Hodgkin's lymphoma in north Cumbria were also covered since some workers at one Scottish nuclear site live over the border in that area. Details of all fathers were then matched against records of the nuclear industry. MAIN OUTCOME MEASURES: Paternal preconceptional radiation exposures, particularly relatively high levels, both lifetime and in the six and three months before conception. RESULTS: No significant excess was observed in any subgroup and there was no significant trend: fathers of three controls but no cases were exposed to lifetime preconceptional levels of 100 mSv or greater (Fisher's exact p value 0.84). In the six months before conception, fathers of two cases and three controls received 10 mSv or more, odds ratio 2.3 (95% confidence interval 0.31 to 17.24). In the three months before conception the fathers of one case and two controls received 5 mSv or more, odds ratio 1.7 (0.10 to 30.76). The results for leukaemia and non-Hodgkin's lymphoma combined were similar. CONCLUSIONS: No significant excess of leukaemia or of leukaemia and non-Hodgkin's lymphoma was found at any radiation level in any preconceptional period.

Rural population mixing and childhood leukaemia: effects of the North Sea oil industry in Scotland, including the area near Dounreay nuclear site.

OBJECTIVE: To determine if any excess of childhood leukaemia and non-Hodgkin's lymphoma was associated with certain striking examples of population mixing in rural Scotland produced by the North Sea oil industry. DESIGN: Details were traced for over 30,000 workers involved in the construction of the large oil terminals in the Shetland and Orkney islands in northern Scotland or employed offshore. Home addresses of the 17,160 Scottish residents were postcoded, integrated with census data, and then classified as urban or rural. Rural postcode sectors, ranked by proportion of oil workers, were grouped into three categories with similar numbers of children but contrasting densities of oil workers. The incidence of leukaemia and non-Hodgkin's lymphoma was examined in these rural (and also in urban) categories in the periods 1974-8, 1979-83 and 1984-8. SETTING: Scotland. SUBJECTS: Young people below age 25. RESULTS: A significant excess of leukaemia and non-Hodgkin's lymphoma was found in 1979-83 in the group of rural home areas with the largest proportion of oil workers, following closely on large increases in the workforce. The area near the Dounreay nuclear installation, where an excess of leukaemia is already well known, was within the rural high oil category. CONCLUSION: The findings support the infection hypothesis that population mixing can increase the incidence of childhood leukaemia in rural areas. They also suggest that the recent excess in the Dounreay-Thurso area is due to population mixing linked to the oil industry, promoted by certain unusual local demographic factors.

Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study.

BACKGROUND: Current use of menopausal hormone therapy (HT) increases the risk of venous thromboembolism (VTE) and the formulations used may affect risk. METHODS: A total of 1,058,259 postmenopausal UK women were followed by record linkage to routinely collected National Health Service hospital admission and death records. HT use and risk of VTE was examined using Cox regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: During 3.3 million years of follow-up, 2200 women had an incident VTE, diagnosed, on average, 1.5 years after last reporting HT use. RRs in current vs. never users at last reporting varied by HT formulation: the risk was significantly greater for oral estrogen-progestin than oral estrogen-only therapy (RR = 2.07 [95%CI, 1.86-2.31] vs. 1.42 [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82 [0.64-1.06]). Among users of oral estrogen-progestin, the risk from HT varied by progestin type, with significantly greater risks for preparations containing medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] vs. 1.91 [1.69-2.17]; Pheterogeneity = 0.0007). Current users of oral HT at last reporting had twice the risk of VTE in the first 2 years after starting HT than later (Pheterogeneity = 0.0006). Associations were similar for deep vein thrombosis with and without pulmonary embolism. Over 5 years, 1 in 660 who had never used HT were admitted to hospital for (or died from) pulmonary embolism, compared with 1 in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate. CONCLUSIONS: The risk of VTE varied considerably by HT formulation, being greatest in users of oral estrogen-progestin HT, especially formulations containing medroxyprogesterone acetate.

Relationship of height, weight and body mass index to the risk of hip and knee replacements in middle-aged women.

OBJECTIVES: To examine the effect of height, weight and body mass index (BMI) on the risk of hip and knee replacement in middle-aged women. METHODS: In a prospective cohort study 490 532 women aged 50-69 yrs who were recruited in the UK in 1996-2001 were followed over 2.9 yrs for incident primary hip and knee replacements. RESULTS: Height, weight and BMI were all associated with the risk of hip and knee replacement. Comparing the tallest group (>or=170 cm) with the shortest (<155 cm) the relative risks were 1.90 (95%CI 1.55-2.32) for hip replacement and 1.55 (95%CI 1.19-2.00) for knee replacement. Comparing the heaviest group (>or=75 kg) with the lightest (<60 kg) the relative risks of hip and knee replacement were 2.37 (95%CI 2.04-2.75) and 9.71 (95%CI 7.39-12.77), respectively. Comparing obese women (BMI >or= 30 kg/m(2)) to women with a BMI < 22.5 kg/m(2), the relative risks for hip and knee replacement were 2.47 (95%CI 2.11-2.89) and 10.51 (95%CI 7.85-14.08), respectively. These effects did not vary according to age, education, alcohol and tobacco consumption, or with use of hormonal therapies. Currently, an estimated 27% of hip replacements and 69% of knee replacements in middle-aged women in the UK are attributable to obesity. CONCLUSION: In middle-aged women, the risk of having a hip or knee replacement increases with both increasing height and increasing BMI. From a clinical perspective, relatively small increases in average BMI among middle-aged women are likely to have a substantial impact on the already increasing rates of joint replacement in the UK.

Infective cause of childhood leukaemia and wartime population mixing in Orkney and Shetland, UK.

In Orkney and Shetland (the UK's northernmost islands), during World War II, local people were outnumbered by servicemen stationed there in case of a northern invasion. Such rural-urban population mixing promotes contact between susceptible and infected individuals. We compared childhood leukaemia mortality in wartime and postwar cohorts of Orkney and Shetland children. Childhood leukaemia increased 3.6-fold, (p=0.001) in the wartime, but not in the postwar, cohort compared with national Scottish rates. These findings add to the evidence for infection as a cause of childhood leukaemia.

Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease.

The incidence of various cancers, especially non-Hodgkin lymphoma (NHL), is higher among patients who receive azathioprine for immunosuppression after organ transplants than in the general population. We have studied the risk of neoplasia after azathioprine in 755 patients treated for inflammatory bowel disease. The patients received 2 mg/kg daily for a median of 12.5 months (range 2 days to 15 years) between 1962 and 1991; median follow-up was 9 years (range 2 weeks to 29 years). Overall there was no significant excess of cancer: 31 azathioprine-treated patients developed cancer before age 85 compared with 24.3 expected from rates in the general population (observed/expected ratio 1.27, p = 0.186). There was a difference in the frequency of colorectal (13) and anal (2) carcinomas (expected 2.27; ratio 6.7, p = 0.00001); these tumours are recognised complications of chronic inflammatory bowel disease. There were 2 cases of invasive cervical cancer (expected 0.5), but no case of NHL. Among patients with extensive chronic ulcerative colitis there was no difference in cancer frequency between 86 who had received azathioprine and 180 matched patients who had never received it. Thus, azathioprine treatment does not substantially increase the risk of cancer in inflammatory bowel disease.