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Cost-Effectiveness in ALTSFindings from the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) triage study (ALTS) suggest that for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing, which refers about half of women to colposcopy, is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cervical cancer as immediate colposcopy for all women. To investigate whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three Pap smears, Kulasingam et al. (p. 92) analyzed data from the ALTS in conjunction with medical cancer costs. The least costly and least effective strategy was conservative management with one Pap test. However, immediate colposcopy and conservative management with up to three Pap tests detected fewer cases of CIN3+ and were either more costly or not as cost-effective as HPV DNA testing. The authors conclude that HPV DNA testing is an economically viable strategy for triage of ASCUS cytology.
In an editorial (p. 82), Melnikow and Birch note that although the cost-effectiveness analysis offers important information to health policy makers and clinicians, cost-effectiveness may miss important societal issues such as patient preferences and use of resources to improve access to health care. They point out that resources applied to ASCUS triage would not be available for other programs.
HSIL and HIV and HPV Infection in Senegalese Women
Because HIV-infected women appear to have an increased risk of developing cervical cancer, Hawes et al. (p. 100) investigated the relationships of human papillomavirus (HPV) infection and persistence, HIV infection, and the development of high-grade cervical squamous intraepithelial lesions (HSILs), precursors to cervical cancer, in a prospective study among Senegalese women. They found that women co-infected with HIV and an oncogenic HPV type were at greatest risk of developing HSIL. Infection (either transient or persistent) with an oncogenic HPV type was strongly associated with development of HSIL. HIV-positive women with low CD4 cell counts or high plasma HIV RNA levels were at increased risk of HSIL. The authors conclude that an increased risk of developing HSIL among HIV-infected women is primarily associated with increased HPV persistence that may be related to immunosuppression induced by HIV infection.
Sex Hormones, Breast Cancer Risk, and Tamoxifen Response
To determine whether sex hormone levels are associated with the effect of tamoxifen on breast cancer risk reduction in a high-risk population, Beattie et al. (p. 110) studied 135 women with postmenopausal breast cancer and 275 postmenopausal women without breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project Cancer Prevention Trial (P-1) and had been treated with either tamoxifen or placebo for 69 months. The authors grouped the women into quartiles by level of plasma estradiol, testosterone, and sex hormone-binding globulin at baseline and estimated breast cancer risk by quartile. They observed no association between risk of breast cancer and sex hormone levels among women in the placebo group. Furthermore, they observed no association between the reduced risk of breast cancer among tamoxifen-treated women, compared with placebo-treated women, and sex hormone levels. The authors conclude that sex hormone levels should not be used to identify women at high risk of breast cancer who are most likely to benefit from chemoprevention with tamoxifen.
Breast Cancer Risk in Icelandic BRCA2 Mutation Carriers
Recent results suggest that the penetrance of BRCA gene mutations has increased over time. Tryggvadóttir et al. (p. 116) examined population-based changes in breast cancer risk over an 80-year period in Icelandic women who carried a specific BRCA2 mutation. Of the 847 breast cancer patients studied, 88 carried the BRCA2 mutation and 759 did not. The cumulative incidence of breast cancer before age 70 years in mutation carriers increased by approximately fourfold. A similar increase was seen in relatives of breast cancer patients who did not carry the BRCA2 mutation, and in the general Icelandic population. During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased only approximately twofold. The authors conclude that changes in penetrance with time should be considered when penetrance is estimated.
IGF1 Genetic Variation and Prostate Cancer Risk
Because insulin-like growth factor I (IGF-I) appears to play a role in the development of prostate cancer, Cheng et al. (p. 123) investigated whether genetic variation in the IGF1 locus was associated with prostate cancer risk. They found no IGF1 missense variants in germline DNA from 95 advanced prostate cancer samples. They found four haplotype blocks with nominally statistically significant associations with prostate cancer risk and two single-nucleotide polymorphisms (SNPs) that were perfectly correlated with each other and were also associated with prostate cancer risk. They determined that these two SNPs were strong proxies for the four haplotype blocks and could account for their haplotype findings. The authors conclude that inherited variation in the IGF1 gene may play a role in the risk of prostate cancer.
Diabetes Mellitus and Colorectal Cancer
Individuals with type 2 diabetes have peripheral resistance to insulin and develop hyperinsulinemia as a compensatory response. Epidemiologic data suggest that a history of diabetes and impaired glucose tolerance are risk factors for colorectal cancer. To investigate the relationship between diabetes and colorectal cancer, Seow et al. (p. 135) analyzed data on more than 63,000 Singapore Chinese men and women who provided information on diet, medical history, and lifestyle at baseline. A history of physician-diagnosed diabetes was statistically significantly associated with colorectal cancer risk in both men and women. The association remained statistically significant among the subset of diabetics with high total calorie intake and low physical activity levels. The authors conclude that hyperinsulinemia may play a role in colorectal carcinogenesis in a relatively lean population.
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