BACKGROUND: The mechanism underlying the role of UV light exposure from sunlight in the etiology of cutaneous malignant melanoma (CMM) is unclear. Patients with xeroderma pigmentosum, a disease characterized by severe sensitivity to UV radiation and a defect in nucleotide excision repair, have a high incidence of CMM, which suggests that DNA repair capacity (DRC) plays a role in sunlight-induced CMM in the general population as well. METHODS: We conducted a hospital-based case-control study of DRC and CMM among 312 non-Hispanic white CMM patients who had no prior chemotherapy or radiation therapy, and 324 cancer-free control subjects who were frequency-matched to case patients on age, sex, and ethnicity. Information on demographic variables, risk factors, and tumor characteristics was obtained from questionnaires and medical records. We used the host-cell reactivation assay to measure the DRC in study subjects' lymphocytes. All statistical tests were two sided. RESULTS: Case patients had a 19% lower mean (+/- standard deviation [SD]) DRC (8.5 +/- 3.4%) than control subjects (10.5 +/- 5.1%), a statistically significant difference (P<.001). DRC that was at or below the median value (i.e., 9.4%) in control subjects was associated with increased risk for CMM after adjustment for age, sex, and other covariates (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.45 to 2.82). We observed a dose-response relationship between decreased DRC and increased risk of CMM (P(trend)<.001). Patients with tumors on sun-exposed skin had statistically significantly lower DRC than patients with tumors on unexposed skin (8.2 +/- 3.3% versus 9.5 +/- 3.5%; P =.004). CONCLUSIONS: Reduced DRC is an independent risk factor for CMM and may contribute to susceptibility to sunlight-induced CMM among the general population.
BACKGROUND: The mechanism underlying the role of UV light exposure from sunlight in the etiology of cutaneous malignant melanoma (CMM) is unclear. Patients with xeroderma pigmentosum, a disease characterized by severe sensitivity to UV radiation and a defect in nucleotide excision repair, have a high incidence of CMM, which suggests that DNA repair capacity (DRC) plays a role in sunlight-induced CMM in the general population as well. METHODS: We conducted a hospital-based case-control study of DRC and CMM among 312 non-Hispanic white CMMpatients who had no prior chemotherapy or radiation therapy, and 324 cancer-free control subjects who were frequency-matched to case patients on age, sex, and ethnicity. Information on demographic variables, risk factors, and tumor characteristics was obtained from questionnaires and medical records. We used the host-cell reactivation assay to measure the DRC in study subjects' lymphocytes. All statistical tests were two sided. RESULTS: Case patients had a 19% lower mean (+/- standard deviation [SD]) DRC (8.5 +/- 3.4%) than control subjects (10.5 +/- 5.1%), a statistically significant difference (P<.001). DRC that was at or below the median value (i.e., 9.4%) in control subjects was associated with increased risk for CMM after adjustment for age, sex, and other covariates (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.45 to 2.82). We observed a dose-response relationship between decreased DRC and increased risk of CMM (P(trend)<.001). Patients with tumors on sun-exposed skin had statistically significantly lower DRC than patients with tumors on unexposed skin (8.2 +/- 3.3% versus 9.5 +/- 3.5%; P =.004). CONCLUSIONS: Reduced DRC is an independent risk factor for CMM and may contribute to susceptibility to sunlight-induced CMM among the general population.
Authors: Xiaohui Tan; Sarah L Anzick; Sikandar G Khan; Takahiro Ueda; Gary Stone; John J Digiovanna; Deborah Tamura; Daniel Wattendorf; David Busch; Carmen C Brewer; Christopher Zalewski; John A Butman; Andrew J Griffith; Paul S Meltzer; Kenneth H Kraemer Journal: Hum Mutat Date: 2013-06-03 Impact factor: 4.878
Authors: Li-E Wang; Ming Yin; Qiong Dong; David J Stewart; Kelly W Merriman; Christopher I Amos; Margaret R Spitz; Qingyi Wei Journal: J Clin Oncol Date: 2011-09-26 Impact factor: 44.544
Authors: Meilin Wang; Hongliang Liu; Zhensheng Liu; Xiaohua Yi; Heike Bickeboller; Rayjean J Hung; Paul Brennan; Maria Teresa Landi; Neil Caporaso; David C Christiani; Jennifer Anne Doherty; Christopher I Amos; Qingyi Wei Journal: Carcinogenesis Date: 2016-06-10 Impact factor: 4.944
Authors: Chunying Li; Hui Zhao; Zhibin Hu; Zhensheng Liu; Li-E Wang; Jeffrey E Gershenwald; Victor G Prieto; Jeffrey E Lee; Madeleine Duvic; Elizabeth A Grimm; Qingyi Wei Journal: Hum Mutat Date: 2008-12 Impact factor: 4.878