Denglong Wu

Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4

Prostate cancer risk–associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk–associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10−14) and 19q13.4 (rs103294, P = 5.34 × 10−16) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10−4). These findings may advance the understanding of genetic susceptibility to prostate cancer.

A novel Germline mutation in HOXB13 is associated with prostate cancer risk in Chinese men

A rare mutation G84E in HOXB13 was recently identified to be associated with prostate cancer (PCa) in Caucasians. The goal of this study is to test association between HOXB13 genetic variants and PCa risk in Chinese men.

Variant allele of HSD3B1 increases progression to castration‐resistant prostate cancer

3β‐hydroxysteroid dehydrogenase type 1 (3βHSD1), which is a rate‐limiting enzyme that catalyzes the conversion of adrenal‐derived steroid dehydroepiandrosterone to dihydrotestosterone (DHT), may be a promising target for treating castration‐resistant prostate cancer (CRPC).

Preliminary study of the homologous recombination repair pathway in mouse spermatogonial stem cells

The present study was designed to detect DNA repair response through the homologous recombination pathway in mouse spermatogonial stem cells. Mouse spermatogonial stem cells (mSSCs) were obtained from the adult DBA/2 mouse testes by MACS sorting. mSSCs and mice animals were divided into four groups (30 min, 2, 24 h, control) and treated with ionizing irradiation while the control group received pseudo‐irradiation. Proteins involved in the homologous recombination pathway (γH2AX, ATM, RAD51, CtIP, and RPA2) were assessed in mSSCs both in vitro and in vivo. Moreover, the non‐homologous end‐joining or homologous recombination (NHEJ/HR) reporter plasmids were transfected into mSSCs to assess NHEJ/HR pathway activity after DNA double‐strand break (DSB). γH2AX, a classical DNA DSB marker, was absent in mSSCs both in vivo and in vitro after DSB repair, but was highly expressed in other tissue stem cells. In addition, ATM and phosphorylated ATM (p‐ATM) were involved in DNA damage response (DDR) in mSSCs. p‐ATM foci were overexpressed immediately after irradiation (30 min and 2 h), but gradually decreased over the repair time. The HR pathway‐related proteins, CtIP and RPA2 were negatively regulated after treatment in Western blot (WB). NHEJ/HR reporter plasmid transfection indicated that the HR pathway played a minor role in mSSCs during DDR, consistent with the WB findings. This study demonstrates that mSSCs may have a unique response to DNA damage since crucial proteins involved in HR pathway were negatively regulated after DSB. In addition, the expression level of p‐ATM, but not γH2AX, was increased after DSB, suggesting that DNA damage repair in mSSCs might be a γH2AX‐independent response. Furthermore, the HR pathway may play a minor role during DDR in mSSCs.

Metastasis to scrotal skin as the initial manifestation in a patient with rectal adenocarcinoma: a rare case report and literature review.

adenocarcinomas have a higher occurrence to give rise to cutaneous scrotum metastases. The first case of cutaneous scrotum metastasis was reported in 1939. Until now, only 40 such cases had been published in the literature written in Chinese and English (Supplementary Table 1). The mean reported patient age was 55.5 years, range from 2 years old to 84 years old. The most frequent symptom was cutaneous nodules, which happened in 24 patients. Another manifestation included papules, plaques, edema, and ulcer. Skin lesions have been reported in seven patients. Some patients complained of pain associated with ulcer, while others were just painless ulcer or nodules. The gastrointestinal system was the most common organ system metastasized to scrotum skin (17 patients). The urogenital system was the second most frequent sites of cancer origin responsible for cutaneous scrotum metastasis (14 patients), which included prostate, bladder, kidney and urethra. The median interval between diagnosis of the primary tumor and subsequent metastasis to the scrotum was just 6 months (range 1–27 months). In addition to single case reports, we reviewed larger case series, which contained data regarding cutaneous metastases. In two series of patients performed by Lookingbill et al.3,5 1420 (10.4%) of 4020 patients were found to have skin involvement. However, just one case had metastasized to the scrotum skin. Reingold4 analyzed that 32 of their 2300 patients with carcinoma had cutaneous metastases. However, no case metastasized to the scrotum skin. The scrotum and penile skin are organs that rarely develop metastases. Maestro et al.6 speculates there are two theories have been postulated to explain this low frequency of metastasis, while their rich vascularization (blood and lymphatic) should result in the opposite. First, perhaps the scrotum and penis have a distinctive defense mechanism, which is not yet discovered (similar to the spleen). Second, these patients with advanced stages of disseminated neoplastic disease pay little attention to the exploration and evaluation of the scrotum and penis, even where a nodule is discovered. The diagnosis of cutaneous scrotum metastases is based on clinical suspicion and physical examination, but the best diagnostic method is biopsy or surgical specimen.6 Treatment depends on the location, size, symptomatology and patient’s prognosis and so on, but average survival in these patients is generally short due to metastatic progression. Treatment may consist of local tumor excision, radiation therapy, and radical surgical procedures for cutaneous scrotum metastatic Dear Editor, We present here a rare case of rectal adenocarcinoma metastasized to scrotum skin that was detected in a 36-year-old man. In addition, we have reviewed the Chinese and English literature for reports of internal malignancy secondary to scrotum skin. To our best knowledge, there are forty cases reported in literature. Rectal adenocarcinoma mainly metastasizes to the lymph nodes, liver, lung and bone.1 Cutaneous metastasis of rectal carcinoma is rare, which mostly occur in the skin of the abdomen and crissum. Scrotum skin is rarely involved. Cutaneous metastasis is generally an indication of widespread disease.2 A 36-year-old male patient was admitted to our hospital due to the swelling of the scrotum in July 2012. The patient had been undergone with lymphadenectomy due to bubo when he was a child. Some scars could be seen in his bilateral legs (Figure 1a). In March 2010, he had been treated with rectal resection and Colocutaneous colostomy due to colorectal adenocarcinoma in another hospital. The patient complained of dysuria as well as the pain of scrotum and penis more than 1-month prior to the visit. The physical examination revealed the multiple papules in the scrotum with obvious tenderness, and enlargement of the inguinal lymph nodes (Figure 1a). About 2 weeks later, the scrotum papules and plaques began to ulcerate and involved in the penis. Biopsies of the ulcer confirmed metastatic adenocarcinoma that was infiltrating the scrotum skin (Figure 1b). Tumor is immunoreactive for CK7 and CK20 (Figure 1c and 1d). No other distance organs were involved by CT. The patient was subsequently treated with suprapubic urinary diversion and two cycles of chemotherapy consisting of gemcitabine and docetaxel. Then, he refused to accept treatment further and was dead due to liver metastasis after discovering scrotum skin metastasis for 1 year. Cutaneous metastases originating from internal malignancies are uncommon.3 The most probable sites of cutaneous metastases are the skin of the anterior chest, followed by the abdomen and back.4 Scrotum skin is unusual invaded. Compared with other histologic subtypes, LETTER TO THE EDITOR